j trejo - Academia.edu (original) (raw)

Papers by j trejo

Research paper thumbnail of A direct role for protein kinase C and the transcription factor Jun/AP-1 in the regulation of the Alzheimer's beta-amyloid precursor protein gene

Journal of Biological Chemistry, 1994

Overexpression of the p-amyloid precursor protein gene (p-APP) may contribute to the abnormal gen... more Overexpression of the p-amyloid precursor protein gene (p-APP) may contribute to the abnormal generation of @-amyloid protein in Alzheimer's disease. We demonstrate using a human glial cell line (1321N1) that activation of protein kinase C (PKC) with phorbol 12myristate 13-acetate (PMA) increases p-APP mRNA levels, induces known components of the transcription factor activator protein-1 (AP-11, and increases protein-DNA binding activity t o m-1 sequences within the PAPP promoter. A p-APP promoter-luciferase reporter gene is transcriptionally activated by PMA, as well as by expression of constitutively activated PKC or by expression of c-Jun. Further characterization suggests that the distal but not the proximal AP-1 recognition site binds nuclear proteins regulated by PKC, and that them-1 binding activity is likely to be composed of Jun-Jun homodimers rather than Jun-Fos heterodimers. Additional studies demonstrate that a single copy of the distal m-1 site fused to a heterologous promoter is sufficient to confer a response to PMA. Mutagenesis of this site in the B-APP promoter renders it unresponsive to c-Jun and attenuates transcriptional activation by PMA. We suggest that cellular mediators that activate PKC, particularly those that induce significant increases in c-Jun, may up-regulate expression of the p-APP gene and consequently affect production and processing of this protein. In Alzheimer's disease there is marked cerebral p-amyloid protein deposition in senile plaques and in the cerebrovasculature (see Ref. 1 for review). The p-amyloid @-A41 protein, is synthesized as part of a larger amyloid precursor protein (p-APP)' that is processed by a "secretase" which cleaves the molecule within the P-amyloid domain inhibiting the release of payment of page charges. This article must therefore be hereby marked

Research paper thumbnail of Biphasic increase in c-jun mRNA is required for induction of AP-1-mediated gene transcription: differential effects of muscarinic and thrombin receptor activation

Molecular and Cellular Biology, 1992

Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turn... more Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases in c-fos mRNA and c-jun mRNA in 1321N1 cells. To determine whether the increases in c-fos and c-jun mRNA induced by carbachol and thrombin are sufficient to stimulate AP-1-mediated transactivation, 1321N1 cells were transfected with a reporter carrying two copies of the tetradecanoyl phorbol acetate response element and the firefly luciferase gene. Thrombin was significantly more effective than carbachol at stimulating AP-1-mediated transactivation. To identify the factors underlying the difference in AP-1 activity induced by carbachol and thrombin, members of the fos and jun families which encode components of AP-1 were examined. Carbachol and thrombin have similar effects on expression of c-fos, fosB, fra-2, junB, and junD, both acutely and over a 24-h time course. However, whereas car...

Research paper thumbnail of Chapter 3 Multiple pathways for signal transduction through the muscarinic cholinergic receptor

Progress in Brain Research, 1990

Publisher Summary This chapter describes the multiple pathways for signal transduction through th... more Publisher Summary This chapter describes the multiple pathways for signal transduction through the muscarinic cholinergic receptor (mAChR). There are three pharmacologically distinct mAChR subtypes, which appear to correspond to the receptors encoded by the M 1 , M 2 , and M 3 genes. The 1321N1 astrocytoma cell has muscarinic receptors that stimulate the cascade of responses typically associated with the actions of Ca 2+ -mobilizing hormones. The active isomer of InsP 3 is formed, Ca 2+ is released from intracellular stores, diacylglycerol is elevated, and protein base C is redistributed to the membrane. Two additional cellular responses are activated, apparently as a consequence of the activation of protein kinase C. First, mAChR stimulation increases the hydrolysis of phosphatidylcholine by a phospholipase D, resulting in the formation of choline and phosphatidic acid. The choline formed from phosphatidylcholine (PC) is important in ACh synthesis under certain conditions. The second consequence of protein kinase C (PKC) activation described in the chapter is an increase in c-fos mRNA. The possibility that the increase in c-fos serves as a “third messenger” for the induction of other gene products, particularly growth factors that may be secreted from astrocytes when they are stimulated, are examined.

Research paper thumbnail of Proteases Display Biased Agonism at Protease-Activated Receptors: Location matters!

Molecular Interventions, 2009

P rotease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that transmit cellul... more P rotease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that transmit cellular responses begun by the actions of extracellular proteases. The activation of a PAR occurs by a unique mechanism whereby the extracellular N-terminal segment of the inactive receptor undergoes proteolytic cleavage, resulting in irreversible activation-unlike most GPCRs that are reversibly activated. PARs mediate cellular responses to coagulant proteases in various cell types localized within the vasculature. Additionally, PARs are expressed in other cell types and respond to a plethora of proteases. Recent studies have revealed that different proteases elicit distinct responses through the activation of the same PAR. This phenomenon appears to involve stabilization of distinct active PAR conformations that facilitates selectively coupling to different effectors and is localized to caveolae, a subtype of lipid rafts.

Research paper thumbnail of A direct role for protein kinase C and the transcription factor Jun/AP-1 in the regulation of the Alzheimer's beta-amyloid precursor protein gene

Journal of Biological Chemistry, 1994

Overexpression of the p-amyloid precursor protein gene (p-APP) may contribute to the abnormal gen... more Overexpression of the p-amyloid precursor protein gene (p-APP) may contribute to the abnormal generation of @-amyloid protein in Alzheimer's disease. We demonstrate using a human glial cell line (1321N1) that activation of protein kinase C (PKC) with phorbol 12myristate 13-acetate (PMA) increases p-APP mRNA levels, induces known components of the transcription factor activator protein-1 (AP-11, and increases protein-DNA binding activity t o m-1 sequences within the PAPP promoter. A p-APP promoter-luciferase reporter gene is transcriptionally activated by PMA, as well as by expression of constitutively activated PKC or by expression of c-Jun. Further characterization suggests that the distal but not the proximal AP-1 recognition site binds nuclear proteins regulated by PKC, and that them-1 binding activity is likely to be composed of Jun-Jun homodimers rather than Jun-Fos heterodimers. Additional studies demonstrate that a single copy of the distal m-1 site fused to a heterologous promoter is sufficient to confer a response to PMA. Mutagenesis of this site in the B-APP promoter renders it unresponsive to c-Jun and attenuates transcriptional activation by PMA. We suggest that cellular mediators that activate PKC, particularly those that induce significant increases in c-Jun, may up-regulate expression of the p-APP gene and consequently affect production and processing of this protein. In Alzheimer's disease there is marked cerebral p-amyloid protein deposition in senile plaques and in the cerebrovasculature (see Ref. 1 for review). The p-amyloid @-A41 protein, is synthesized as part of a larger amyloid precursor protein (p-APP)' that is processed by a "secretase" which cleaves the molecule within the P-amyloid domain inhibiting the release of payment of page charges. This article must therefore be hereby marked

Research paper thumbnail of Biphasic increase in c-jun mRNA is required for induction of AP-1-mediated gene transcription: differential effects of muscarinic and thrombin receptor activation

Molecular and Cellular Biology, 1992

Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turn... more Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases in c-fos mRNA and c-jun mRNA in 1321N1 cells. To determine whether the increases in c-fos and c-jun mRNA induced by carbachol and thrombin are sufficient to stimulate AP-1-mediated transactivation, 1321N1 cells were transfected with a reporter carrying two copies of the tetradecanoyl phorbol acetate response element and the firefly luciferase gene. Thrombin was significantly more effective than carbachol at stimulating AP-1-mediated transactivation. To identify the factors underlying the difference in AP-1 activity induced by carbachol and thrombin, members of the fos and jun families which encode components of AP-1 were examined. Carbachol and thrombin have similar effects on expression of c-fos, fosB, fra-2, junB, and junD, both acutely and over a 24-h time course. However, whereas car...

Research paper thumbnail of Chapter 3 Multiple pathways for signal transduction through the muscarinic cholinergic receptor

Progress in Brain Research, 1990

Publisher Summary This chapter describes the multiple pathways for signal transduction through th... more Publisher Summary This chapter describes the multiple pathways for signal transduction through the muscarinic cholinergic receptor (mAChR). There are three pharmacologically distinct mAChR subtypes, which appear to correspond to the receptors encoded by the M 1 , M 2 , and M 3 genes. The 1321N1 astrocytoma cell has muscarinic receptors that stimulate the cascade of responses typically associated with the actions of Ca 2+ -mobilizing hormones. The active isomer of InsP 3 is formed, Ca 2+ is released from intracellular stores, diacylglycerol is elevated, and protein base C is redistributed to the membrane. Two additional cellular responses are activated, apparently as a consequence of the activation of protein kinase C. First, mAChR stimulation increases the hydrolysis of phosphatidylcholine by a phospholipase D, resulting in the formation of choline and phosphatidic acid. The choline formed from phosphatidylcholine (PC) is important in ACh synthesis under certain conditions. The second consequence of protein kinase C (PKC) activation described in the chapter is an increase in c-fos mRNA. The possibility that the increase in c-fos serves as a “third messenger” for the induction of other gene products, particularly growth factors that may be secreted from astrocytes when they are stimulated, are examined.

Research paper thumbnail of Proteases Display Biased Agonism at Protease-Activated Receptors: Location matters!

Molecular Interventions, 2009

P rotease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that transmit cellul... more P rotease-activated receptors (PARs) are G protein-coupled receptors (GPCRs) that transmit cellular responses begun by the actions of extracellular proteases. The activation of a PAR occurs by a unique mechanism whereby the extracellular N-terminal segment of the inactive receptor undergoes proteolytic cleavage, resulting in irreversible activation-unlike most GPCRs that are reversibly activated. PARs mediate cellular responses to coagulant proteases in various cell types localized within the vasculature. Additionally, PARs are expressed in other cell types and respond to a plethora of proteases. Recent studies have revealed that different proteases elicit distinct responses through the activation of the same PAR. This phenomenon appears to involve stabilization of distinct active PAR conformations that facilitates selectively coupling to different effectors and is localized to caveolae, a subtype of lipid rafts.