Drs Brock and Fernette Eide (original) (raw)
Papers by Drs Brock and Fernette Eide
Biochemistry, Oct 1, 1986
Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies ... more Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies reactive against guanine nucleotide binding proteins (G proteins) that had been mono-ADPribosylated by bacterial toxins. Antibody reactivity on immunoblots was strictly dependent on incubation
Journal of Trauma-injury Infection and Critical Care, Apr 1, 1983
Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perf... more Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perform limited intravenous pyelography (IVP), usually with cystography, in such individuals presenting with any degree of hematuria in order to identify urinary tract injury. The observation that the yield of positive IVPs is small among such individuals, and the suspicion that a positive IVP rarely leads to a substantive change in outcome, resulted in the following retrospective study. We reviewed our Trauma Center's records for all patients undergoing IVP following blunt trauma in a 1-year period. Virtually all individuals had a cystogram performed. Positive studies were defined by various kidney, ureteral, bladder, or urethral abnormalities; bladder deviation by extrinsic pelvic hematoma was not counted as a positive finding. Among 156 patients undergoing IVP for hematuria in this period, 13 (8.3%) had an abnormal IVP or cystogram. Of these 13 patients ten (77%) had either gross or 4+ hematuria. Five patients (3%) required further diagnostic or therapeutic intervention. One patient (0.6%) required nephrectomy when exploration revealed renal artery thrombosis causing irreversible kidney ischemia. All five patients who required further evaluation or therapy presented with gross or 4+ hematuria. Had screening IVP been performed only in blunt trauma victims presenting with gross or 4+ hematuria, no patients with significant urinary tract injury would have been missed, and 119 (75%) of the patients in this series would have been spared the expenditure of time and money, and the radiation and dye exposure, resulting from their negative studies. Individuals in whom the possibility of renal injury is high following blunt trauma (flank pain or hematoma, low rib fractures) should undergo rapid limited IVP for diagnosis of significant genitourinary tract injury. Such evaluation should also be carried out in asymptomatic individuals who present with gross or 4+ hematuria. Microscopic hematuria alone, however, is a poor predictor of significant genitourinary tract damage. Our review suggests that asymptomatic victims of blunt trauma who have only small amounts of blood in the urine may safely be observed without routine emergency IVP.
Duke University Press eBooks, Oct 13, 1999
The American Journal of Surgery, 1983
Death from variceal hemorrhage is a common outcome for patients with portal hypertension arising ... more Death from variceal hemorrhage is a common outcome for patients with portal hypertension arising from hepatic cirrhosis. Usually resulting from alcohol-induced liver disease, this condition currently ranks as the seventh leading cause of death in the United States [I], and is one of the few which has had a significant increase in incidence over the past 3 decades. Its victims are most frequently in the 35 to 64 year age group-thus potentially socially and economically productive. The health care costs for the management of patients with variceal hemorrhage are staggering. O'Donnell et al [2] have demonstrated hospital costs of more than $35,000 per bleeding episode. Shunting procedures for decompression of the portal system have been employed extensively since their popularization by Blakemore and Lord [3] and Whipple [4] in 1945. Unfortunately, although it is clear that the incidence of both recurrent variceal hemorrhage and death after exsanguination from ruptured varices can be reduced markedly by various forms of portal decompression, this benefit appears to be neutralized by a sharply increased incidence of liver failure in shunted patients. Thus, no properly performed analysis testing the hypothesis that shunts prolong survival after variceal hemorrhage has achieved statistical significance on the side of operation, although a clear trend, suggesting perhaps a 20 percent prolongation of life with shunt surgery, is evident in virtually all of these studies. Orloff et al [5,6] have promoted emergency portacaval shunting in patients bleeding from varices,
... Instead, Doug, Lindsey, and Peteand millions of individuals with dyslexia just like themare... more ... Instead, Doug, Lindsey, and Peteand millions of individuals with dyslexia just like themare good at what they ... Richard Branson, singer-songwriter John Lennon, paleontologist Jack Horner, financial services pioneer Charles Schwab, inventor Dean Kamen, architect Richard ...
Biochemistry, 1986
Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies ... more Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies reactive against guanine nucleotide binding proteins (G proteins) that had been mono-ADPribosylated by bacterial toxins. Antibody reactivity on immunoblots was strictly dependent on incubation
A number of cellular processes, such as proliferation, differentiation, and transformation, are r... more A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125 FAK , as a component of cell adhesion plaques. p125 FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125 FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125 FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125 FAK and that this association prevents dephosphorylation of pp125 FAK in vitro by protein tyrosine phosphatases. In this report, we identify Tyr-397 as the primary in vivo and in vitro site of p125 FAK tyrosine phosphorylation and association with Src. Substituting phenylalanine for tyrosine at position 397 significantly reduces p125 FAK tyrosine phosphorylation and association with Src but does not abolish p125 FAK kinase activity. In addition, p125 FAK kinase is able to trans-phosphorylate Tyr-397 in vitro in a kinase-deficient p125 FAK variant. Phosphorylation of Tyr-397 provides a site [Y (P) AEI] that fits the consensus sequence for the binding of Src.
The Journal of Neuroscience
trkB encodes a receptor tyrosine kinase activated by three neurotrophins-brain-derived neurotroph... more trkB encodes a receptor tyrosine kinase activated by three neurotrophins-brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In viva, three isoforms of the receptor are generated by differential splicing-gpl 45f'kB or the full-length trkB receptor, and trkB.Tf and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.Tl, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145frks, but not trkB.Tl or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-y-mediated mechanism) after stimulation by BDNF. When trkB.Tl and trkB.TZ were coexpressed with gpl 45trkB, they acted as dominant negative receptors, inhibiting the BDNF signal by forming nonfunctional heterodimers with the full-length receptors. An ATP-binding mutant of gpl 4PkB had similar dominant inhibitory effects. Our data suggest that naturally occurring truncated trkB receptors function as inhibitory modulators of neurotrophin responsiveness. Furthermore, the homodimerization of gpl 45frkB appears to be an essential step in activation of the BDNF signaling cascade.
Nature Clinical Practice Neurology, Aug 1, 2006
Nature Clinical Practice Neurology will deliver timely interpretations of key research developmen... more Nature Clinical Practice Neurology will deliver timely interpretations of key research developments, translating the latest findings into clinical practice. Our Editor-in-Chief and international Advisory Board will ensure comprehensive coverage of topical issues throughout the year, with ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1996
trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrop... more trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In vivo, three isoforms of the receptor are generated by differential splicing--gp145trkB or the full-length trkB receptor, and trkB.T1 and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.T1, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145trkB, but not trkB.T1 or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-gamma-mediated mechanism) after stimulation by BDNF. When trkB.T1 and trkB.T2 were coexpressed with gp145trk...
Molecular and cellular biology, 1995
A number of cellular processes, such as proliferation, differentiation, and transformation, are r... more A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125FAK, as a component of cell adhesion plaques. p125FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125FAK and that this ...
Molecular and cellular endocrinology, 1987
High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are ch... more High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupli...
Nature Clinical Practice Neurology, 2006
Nature Clinical Practice Neurology will deliver timely interpretations of key research developmen... more Nature Clinical Practice Neurology will deliver timely interpretations of key research developments, translating the latest findings into clinical practice. Our Editor-in-Chief and international Advisory Board will ensure comprehensive coverage of topical issues throughout the year, with ...
Molecular and Cellular Endocrinology, 1987
High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are ch... more High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupling rhodopsin to cGMP phosphodiesterase in rod photoreceptors (Bitensky, M.W. et al. (1981) Curr. Top. Membr. Transp. 15, 237-271; Stryer, L. (1986) Annu. Rev. Neurosci. 9, 87-119), and Go, a G-protein of unknown function that is highly abundant in brain (Sternweis, P.C. and Robishaw, J.D. (1984) J. Biol. Chem. 259, 13806-13813; Neer, E.J. et al. (1984) J. Biol. Chem. 259, 14222-14229). G-proteins also participate in other signal transduction pathways, notably that involving phosphoinositide breakdown. In this review, I highlight recent progress in our understanding of the structure, function, and diversity of G-proteins.
The Journal of Emergency Medicine, 1984
Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perf... more Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perform limited intravenous pyelography (IVP), usually with cystography, in such individuals presenting with any degree of hematuria in order to identify urinary tract injury. The observation that the yield of positive IVPs is small among such individuals, and the suspicion that a positive IVP rarely leads to a substantive change in outcome, resulted in the following retrospective study. We reviewed our Trauma Center's records for all patients undergoing IVP following blunt trauma in a 1-year period. Virtually all individuals had a cystogram performed. Positive studies were defined by various kidney, ureteral, bladder, or urethral abnormalities; bladder deviation by extrinsic pelvic hematoma was not counted as a positive finding. Among 156 patients undergoing IVP for hematuria in this period, 13 (8.3%) had an abnormal IVP or cystogram. Of these 13 patients ten (77%) had either gross or 4+ hematuria. Five patients (3%) required further diagnostic or therapeutic intervention. One patient (0.6%) required nephrectomy when exploration revealed renal artery thrombosis causing irreversible kidney ischemia. All five patients who required further evaluation or therapy presented with gross or 4+ hematuria. Had screening IVP been performed only in blunt trauma victims presenting with gross or 4+ hematuria, no patients with significant urinary tract injury would have been missed, and 119 (75%) of the patients in this series would have been spared the expenditure of time and money, and the radiation and dye exposure, resulting from their negative studies. Individuals in whom the possibility of renal injury is high following blunt trauma (flank pain or hematoma, low rib fractures) should undergo rapid limited IVP for diagnosis of significant genitourinary tract injury. Such evaluation should also be carried out in asymptomatic individuals who present with gross or 4+ hematuria. Microscopic hematuria alone, however, is a poor predictor of significant genitourinary tract damage. Our review suggests that asymptomatic victims of blunt trauma who have only small amounts of blood in the urine may safely be observed without routine emergency IVP.
Journal of Cellular Physiology, 1986
Preincubation of Swiss 3T3 cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (T... more Preincubation of Swiss 3T3 cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) at 37 degrees C is observed to cause only a small (approximately 10%) decrease in maximal binding of 125I-platelet-derived growth factor (125I-PDGF), and does not affect the affinity of 125I-PDGF binding to these cells. Under the same conditions, the affinity of the epidermal growth factor receptor is greatly reduced, possibly resulting from phosphorylation by protein kinase C. TPA is also shown to have no effect on the kinetics of internalization or degradation of bound 125I-PDGF. Although TPA has little or no effect on these properties of the PDGF receptor, it was found to act in a synergistic fashion with low, but not high, concentrations of PDGF to increase DNA synthesis by 3T3 cells. Since TPA has previously been shown to activate protein kinase C, these findings suggest that protein kinase C does not regulate the ligand-binding properties of the PDGF receptor, and that the observed synergism between TPA and PDGF in stimulating mitogenesis reflects effects of TPA on other processes in the mitogenic pathway.
Biochemical and Biophysical Research Communications, 1987
Using specific antisera raised against synthetic peptides, we find that three distinct GTP-bindin... more Using specific antisera raised against synthetic peptides, we find that three distinct GTP-binding protein alpha subunits remain bound to the plasma membrane even after activation with nonhydrolyzable GTP analog. Trypsin cleaves each alpha subunit at a site near the amino-terminus, and quantitatively releases the large fragment (comprising all but an amino-terminal 2kDa piece) from the membrane. Our results indicate that alpha subunits are essentially cytoplasmic proteins tethered to the inner surface of the membrane via an amino terminal stalk. ©1987AcademiePress. Ine. GTP-binding proteins (G-proteins) are signal transducers composed of distinct alpha, beta, and gamma subunits. Alpha subunits bind guanine nucleotides, and confer specificity in coupling of receptors and effectors by G-proteins (i). Alpha subunits are widely assumed to be associated with the cytoplasmic surface of the plasma membrane, but there are no data regarding the extent or orientation of their attachment to the membrane IHoward Hughes Medical Institute/NIH Medical Scholars Program. 2To whom correspondence and requests for reprints should be addressed at Bldg. i0, Room 9CI01. Abbreviations: G-proteins, guanine nucleotide binding proteins; Go, a G-protein of unknown function abundant in brain; Gi, a Gprotein initially defined in terms of inhibition of adenylyl cyclase; GTP-gammaS , guanosine 5'-(3-O-thio)-triphosphate; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis.
Understanding Our Gifted, 2009
A major reason why dyslexia is likely to be missed or mislabeled in an intellectually gifted chil... more A major reason why dyslexia is likely to be missed or mislabeled in an intellectually gifted child is the lack of a specific, clearly recognized definition to enable diagnosis of dyslexia. It's crucial that adults working with gifted students understand that average or even above reading ...
Biochemistry, Oct 1, 1986
Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies ... more Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies reactive against guanine nucleotide binding proteins (G proteins) that had been mono-ADPribosylated by bacterial toxins. Antibody reactivity on immunoblots was strictly dependent on incubation
Journal of Trauma-injury Infection and Critical Care, Apr 1, 1983
Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perf... more Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perform limited intravenous pyelography (IVP), usually with cystography, in such individuals presenting with any degree of hematuria in order to identify urinary tract injury. The observation that the yield of positive IVPs is small among such individuals, and the suspicion that a positive IVP rarely leads to a substantive change in outcome, resulted in the following retrospective study. We reviewed our Trauma Center's records for all patients undergoing IVP following blunt trauma in a 1-year period. Virtually all individuals had a cystogram performed. Positive studies were defined by various kidney, ureteral, bladder, or urethral abnormalities; bladder deviation by extrinsic pelvic hematoma was not counted as a positive finding. Among 156 patients undergoing IVP for hematuria in this period, 13 (8.3%) had an abnormal IVP or cystogram. Of these 13 patients ten (77%) had either gross or 4+ hematuria. Five patients (3%) required further diagnostic or therapeutic intervention. One patient (0.6%) required nephrectomy when exploration revealed renal artery thrombosis causing irreversible kidney ischemia. All five patients who required further evaluation or therapy presented with gross or 4+ hematuria. Had screening IVP been performed only in blunt trauma victims presenting with gross or 4+ hematuria, no patients with significant urinary tract injury would have been missed, and 119 (75%) of the patients in this series would have been spared the expenditure of time and money, and the radiation and dye exposure, resulting from their negative studies. Individuals in whom the possibility of renal injury is high following blunt trauma (flank pain or hematoma, low rib fractures) should undergo rapid limited IVP for diagnosis of significant genitourinary tract injury. Such evaluation should also be carried out in asymptomatic individuals who present with gross or 4+ hematuria. Microscopic hematuria alone, however, is a poor predictor of significant genitourinary tract damage. Our review suggests that asymptomatic victims of blunt trauma who have only small amounts of blood in the urine may safely be observed without routine emergency IVP.
Duke University Press eBooks, Oct 13, 1999
The American Journal of Surgery, 1983
Death from variceal hemorrhage is a common outcome for patients with portal hypertension arising ... more Death from variceal hemorrhage is a common outcome for patients with portal hypertension arising from hepatic cirrhosis. Usually resulting from alcohol-induced liver disease, this condition currently ranks as the seventh leading cause of death in the United States [I], and is one of the few which has had a significant increase in incidence over the past 3 decades. Its victims are most frequently in the 35 to 64 year age group-thus potentially socially and economically productive. The health care costs for the management of patients with variceal hemorrhage are staggering. O'Donnell et al [2] have demonstrated hospital costs of more than $35,000 per bleeding episode. Shunting procedures for decompression of the portal system have been employed extensively since their popularization by Blakemore and Lord [3] and Whipple [4] in 1945. Unfortunately, although it is clear that the incidence of both recurrent variceal hemorrhage and death after exsanguination from ruptured varices can be reduced markedly by various forms of portal decompression, this benefit appears to be neutralized by a sharply increased incidence of liver failure in shunted patients. Thus, no properly performed analysis testing the hypothesis that shunts prolong survival after variceal hemorrhage has achieved statistical significance on the side of operation, although a clear trend, suggesting perhaps a 20 percent prolongation of life with shunt surgery, is evident in virtually all of these studies. Orloff et al [5,6] have promoted emergency portacaval shunting in patients bleeding from varices,
... Instead, Doug, Lindsey, and Peteand millions of individuals with dyslexia just like themare... more ... Instead, Doug, Lindsey, and Peteand millions of individuals with dyslexia just like themare good at what they ... Richard Branson, singer-songwriter John Lennon, paleontologist Jack Horner, financial services pioneer Charles Schwab, inventor Dean Kamen, architect Richard ...
Biochemistry, 1986
Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies ... more Rabbits immunized with ADP-ribose chemically conjugated to carrier proteins developed antibodies reactive against guanine nucleotide binding proteins (G proteins) that had been mono-ADPribosylated by bacterial toxins. Antibody reactivity on immunoblots was strictly dependent on incubation
A number of cellular processes, such as proliferation, differentiation, and transformation, are r... more A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125 FAK , as a component of cell adhesion plaques. p125 FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125 FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125 FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125 FAK and that this association prevents dephosphorylation of pp125 FAK in vitro by protein tyrosine phosphatases. In this report, we identify Tyr-397 as the primary in vivo and in vitro site of p125 FAK tyrosine phosphorylation and association with Src. Substituting phenylalanine for tyrosine at position 397 significantly reduces p125 FAK tyrosine phosphorylation and association with Src but does not abolish p125 FAK kinase activity. In addition, p125 FAK kinase is able to trans-phosphorylate Tyr-397 in vitro in a kinase-deficient p125 FAK variant. Phosphorylation of Tyr-397 provides a site [Y (P) AEI] that fits the consensus sequence for the binding of Src.
The Journal of Neuroscience
trkB encodes a receptor tyrosine kinase activated by three neurotrophins-brain-derived neurotroph... more trkB encodes a receptor tyrosine kinase activated by three neurotrophins-brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In viva, three isoforms of the receptor are generated by differential splicing-gpl 45f'kB or the full-length trkB receptor, and trkB.Tf and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.Tl, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145frks, but not trkB.Tl or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-y-mediated mechanism) after stimulation by BDNF. When trkB.Tl and trkB.TZ were coexpressed with gpl 45trkB, they acted as dominant negative receptors, inhibiting the BDNF signal by forming nonfunctional heterodimers with the full-length receptors. An ATP-binding mutant of gpl 4PkB had similar dominant inhibitory effects. Our data suggest that naturally occurring truncated trkB receptors function as inhibitory modulators of neurotrophin responsiveness. Furthermore, the homodimerization of gpl 45frkB appears to be an essential step in activation of the BDNF signaling cascade.
Nature Clinical Practice Neurology, Aug 1, 2006
Nature Clinical Practice Neurology will deliver timely interpretations of key research developmen... more Nature Clinical Practice Neurology will deliver timely interpretations of key research developments, translating the latest findings into clinical practice. Our Editor-in-Chief and international Advisory Board will ensure comprehensive coverage of topical issues throughout the year, with ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1996
trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrop... more trkB encodes a receptor tyrosine kinase activated by three neurotrophins--brain-derived neurotrophic factor (BDNF), neurotrophin-3, and neurotrophin-4/5. In vivo, three isoforms of the receptor are generated by differential splicing--gp145trkB or the full-length trkB receptor, and trkB.T1 and trkB.T2, two cytoplasmically truncated receptors that lack kinases, but contain unique C termini. Although the truncated receptors appear to be precisely regulated during nervous system development and regeneration, their role in neurotrophin signaling has not been directly tested. In this paper, we studied the signaling properties and interactions of gp145trkB, trkB.T1, and trkB.T2 by expressing the receptors in a Xenopus oocyte microinjection assay. We found that oocytes expressing gp145trkB, but not trkB.T1 or trkB.T2, were capable of eliciting 45Ca efflux responses (a phospholipase C-gamma-mediated mechanism) after stimulation by BDNF. When trkB.T1 and trkB.T2 were coexpressed with gp145trk...
Molecular and cellular biology, 1995
A number of cellular processes, such as proliferation, differentiation, and transformation, are r... more A number of cellular processes, such as proliferation, differentiation, and transformation, are regulated by cell-extracellular matrix interactions. Previous studies have identified a novel tyrosine kinase, the focal adhesion kinase p125FAK, as a component of cell adhesion plaques. p125FAK was identified as a 125-kDa tyrosine-phosphorylated protein in cells transformed by the v-src oncogene. p125FAK is an intracellular protein composed of three domains: a central domain with homology to protein tyrosine kinases, flanked by two noncatalytic domains of 400 amino acids which bear no significant homology to previously cloned proteins. p125FAK is believed to play an important regulatory role in cell adhesion because it localizes to cell adhesion plaques and because its phosphorylation on tyrosine residues is regulated by binding of cell surface integrins to the extracellular matrix. Recent studies have shown that Src, through its SH2 domain, stably associates with pp125FAK and that this ...
Molecular and cellular endocrinology, 1987
High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are ch... more High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupli...
Nature Clinical Practice Neurology, 2006
Nature Clinical Practice Neurology will deliver timely interpretations of key research developmen... more Nature Clinical Practice Neurology will deliver timely interpretations of key research developments, translating the latest findings into clinical practice. Our Editor-in-Chief and international Advisory Board will ensure comprehensive coverage of topical issues throughout the year, with ...
Molecular and Cellular Endocrinology, 1987
High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are ch... more High affinity binding of guanine nucleotides and the ability to hydrolyze bound GTP to GDP are characteristics of an extended family of intracellular proteins. Subsets of this family include cytosolic initiation and elongation factors involved in protein synthesis, and cytoskeletal proteins such as tubulin (Hughes, S.M. (1983) FEBS Lett. 164, 1-8). A distinct subset of guanine nucleotide binding proteins is membrane-associated; members of this subset include the ras gene products (Ellis, R.W. et al. (1981) Nature 292, 506-511) and the heterotrimeric G-proteins (also termed N-proteins) (Gilman, A.G. (1984) Cell 36, 577-579). Substantial evidence indicates that G-proteins act as signal transducers by coupling receptors (R) to effectors (E). A similar function has been suggested but not proven for the ras gene products. Known G-proteins include Gs and Gi, the G-proteins associated with stimulation and inhibition, respectively, of adenylate cyclase; transducin (TD), the G-protein coupling rhodopsin to cGMP phosphodiesterase in rod photoreceptors (Bitensky, M.W. et al. (1981) Curr. Top. Membr. Transp. 15, 237-271; Stryer, L. (1986) Annu. Rev. Neurosci. 9, 87-119), and Go, a G-protein of unknown function that is highly abundant in brain (Sternweis, P.C. and Robishaw, J.D. (1984) J. Biol. Chem. 259, 13806-13813; Neer, E.J. et al. (1984) J. Biol. Chem. 259, 14222-14229). G-proteins also participate in other signal transduction pathways, notably that involving phosphoinositide breakdown. In this review, I highlight recent progress in our understanding of the structure, function, and diversity of G-proteins.
The Journal of Emergency Medicine, 1984
Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perf... more Blood in the urine is common following blunt abdominal trauma. Most trauma centers routinely perform limited intravenous pyelography (IVP), usually with cystography, in such individuals presenting with any degree of hematuria in order to identify urinary tract injury. The observation that the yield of positive IVPs is small among such individuals, and the suspicion that a positive IVP rarely leads to a substantive change in outcome, resulted in the following retrospective study. We reviewed our Trauma Center's records for all patients undergoing IVP following blunt trauma in a 1-year period. Virtually all individuals had a cystogram performed. Positive studies were defined by various kidney, ureteral, bladder, or urethral abnormalities; bladder deviation by extrinsic pelvic hematoma was not counted as a positive finding. Among 156 patients undergoing IVP for hematuria in this period, 13 (8.3%) had an abnormal IVP or cystogram. Of these 13 patients ten (77%) had either gross or 4+ hematuria. Five patients (3%) required further diagnostic or therapeutic intervention. One patient (0.6%) required nephrectomy when exploration revealed renal artery thrombosis causing irreversible kidney ischemia. All five patients who required further evaluation or therapy presented with gross or 4+ hematuria. Had screening IVP been performed only in blunt trauma victims presenting with gross or 4+ hematuria, no patients with significant urinary tract injury would have been missed, and 119 (75%) of the patients in this series would have been spared the expenditure of time and money, and the radiation and dye exposure, resulting from their negative studies. Individuals in whom the possibility of renal injury is high following blunt trauma (flank pain or hematoma, low rib fractures) should undergo rapid limited IVP for diagnosis of significant genitourinary tract injury. Such evaluation should also be carried out in asymptomatic individuals who present with gross or 4+ hematuria. Microscopic hematuria alone, however, is a poor predictor of significant genitourinary tract damage. Our review suggests that asymptomatic victims of blunt trauma who have only small amounts of blood in the urine may safely be observed without routine emergency IVP.
Journal of Cellular Physiology, 1986
Preincubation of Swiss 3T3 cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (T... more Preincubation of Swiss 3T3 cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA) at 37 degrees C is observed to cause only a small (approximately 10%) decrease in maximal binding of 125I-platelet-derived growth factor (125I-PDGF), and does not affect the affinity of 125I-PDGF binding to these cells. Under the same conditions, the affinity of the epidermal growth factor receptor is greatly reduced, possibly resulting from phosphorylation by protein kinase C. TPA is also shown to have no effect on the kinetics of internalization or degradation of bound 125I-PDGF. Although TPA has little or no effect on these properties of the PDGF receptor, it was found to act in a synergistic fashion with low, but not high, concentrations of PDGF to increase DNA synthesis by 3T3 cells. Since TPA has previously been shown to activate protein kinase C, these findings suggest that protein kinase C does not regulate the ligand-binding properties of the PDGF receptor, and that the observed synergism between TPA and PDGF in stimulating mitogenesis reflects effects of TPA on other processes in the mitogenic pathway.
Biochemical and Biophysical Research Communications, 1987
Using specific antisera raised against synthetic peptides, we find that three distinct GTP-bindin... more Using specific antisera raised against synthetic peptides, we find that three distinct GTP-binding protein alpha subunits remain bound to the plasma membrane even after activation with nonhydrolyzable GTP analog. Trypsin cleaves each alpha subunit at a site near the amino-terminus, and quantitatively releases the large fragment (comprising all but an amino-terminal 2kDa piece) from the membrane. Our results indicate that alpha subunits are essentially cytoplasmic proteins tethered to the inner surface of the membrane via an amino terminal stalk. ©1987AcademiePress. Ine. GTP-binding proteins (G-proteins) are signal transducers composed of distinct alpha, beta, and gamma subunits. Alpha subunits bind guanine nucleotides, and confer specificity in coupling of receptors and effectors by G-proteins (i). Alpha subunits are widely assumed to be associated with the cytoplasmic surface of the plasma membrane, but there are no data regarding the extent or orientation of their attachment to the membrane IHoward Hughes Medical Institute/NIH Medical Scholars Program. 2To whom correspondence and requests for reprints should be addressed at Bldg. i0, Room 9CI01. Abbreviations: G-proteins, guanine nucleotide binding proteins; Go, a G-protein of unknown function abundant in brain; Gi, a Gprotein initially defined in terms of inhibition of adenylyl cyclase; GTP-gammaS , guanosine 5'-(3-O-thio)-triphosphate; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis.
Understanding Our Gifted, 2009
A major reason why dyslexia is likely to be missed or mislabeled in an intellectually gifted chil... more A major reason why dyslexia is likely to be missed or mislabeled in an intellectually gifted child is the lack of a specific, clearly recognized definition to enable diagnosis of dyslexia. It's crucial that adults working with gifted students understand that average or even above reading ...