CEA adhesion molecules: multifunctional proteins with signal-regulatory properties (original) (raw)

Abstract

The carcinoembryonic antigen family comprises a large number of complex molecules, several of which possess cell adhesion activities. The primordial adhesion molecules of this family are the cell—cell adhesion molecules (C-CAMs), which have been found to be multifunctional, signal-regulatory proteins. C-CAMs inhibit tumor growth, interact with calmodulin, protein tyrosine kinases and protein tyrosine phosphatases, and are subject to specific dimerization reactions. These new insights indicate that C-CAMs are important regulators of cellular functions.

Abbreviations: Bgp biliary glycoprotein in mouse, BGP biliary glycoprotein in man, C-CAM cell—cell adhesion molecule, CEA carcinoembryonic antigen, CGM CEA gene family member, GPI glycosylphosphatidylinositol, Ig immunoglobulin, IgSF Ig gene superfamily, ITAM immunoreceptor tyrosine-based activation motif, ITIM immunoreceptor tyrosine-based inhibition motif, L long, NCA nonspecific cross-reactive antigen, PTK protein tyrosine kinase, PTP protein tyrosine phosphatase, S short, SH Src homology, SHP SH2-domain-containing PTP, SIRP signal-regulatory protein

References

• 1.Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–481. doi: 10.1084/jem.122.3.467. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 2.Thompson JA, Grunert F, Zimmermann W. The carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal. 1991;5:344–366. doi: 10.1002/jcla.1860050510. [DOI] [PubMed] [Google Scholar]
• 3.Öbrink B. C-CAM (Cell-CAM 105) — a member of the growing immunoglobulin superfamily of cell adhesion proteins. Bioessays. 1991;13:227–234. doi: 10.1002/bies.950130505. [DOI] [PubMed] [Google Scholar]
• 4.Stanners CP, Rojas M, Zhou H, Fuks A, Beauchemin N. The CEA family: a system in transitional evolution? Int J Biol Markers. 1992;7:137–142. doi: 10.1177/172460089200700303. [DOI] [PubMed] [Google Scholar]
• 5.Nagel G, Grunert F. From genes to proteins: the nonspecific cross-reacting antigens. Tumour Biol. 1995;16:17–22. doi: 10.1159/000217924. [DOI] [PubMed] [Google Scholar]
• 6.Stanners CP, DeMarte L, Rojas M, Gold P, Fuks A. Opposite functions for two classes of genes of the human carcinoembryonic antigen family. Tumour Biol. 1995;16:23–31. doi: 10.1159/000217925. [DOI] [PubMed] [Google Scholar]
• 7.Nédellec P, Dveksler GS, Daniels E, Turbide C, Chow B, Basile AA, Holmes KV, Beauchemin N. Bgp2, a new member of the carcinoembryonic antigen-related gene family, encodes an alternative receptor for mouse hepatitis viruses. J Virol. 1994;68:4525–4537. doi: 10.1128/jvi.68.7.4525-4537.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 8.Edlund M, Gaardsvoll H, Bock E, Öbrink B. Different isoforms and stock-specific variants of the cell adhesion molecule C-CAM (cell-CAM 105) in rat liver. Eur J Biochem. 1993;213:1109–1116. doi: 10.1111/j.1432-1033.1993.tb17860.x. [DOI] [PubMed] [Google Scholar]
• 9.McCuaig K, Rosenberg M, Nédellec P, Turbide C, Beauchemin N. Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms. Gene. 1993;127:173–183. doi: 10.1016/0378-1119(93)90716-G. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 10.Najjar SM, Accili D, Neubert P, Jernberg J, Margolis RN, Taylor SI. pp120/ectoATPase, an endogenous substrate of the insulin receptor tyrosine kinase, is expressed as two variably spliced isoforms. J Biol Chem. 1993;268:1201–1206. [PubMed] [Google Scholar]
• 11.Odin P, Asplund M, Busch C, Öbrink B. Immunohistochemical localization of cell-CAM 105 in rat tissues. Appearance in epithelia, platelets and granulocytes. J Histochem Cytochem. 1988;36:729–739. doi: 10.1177/36.7.3290331. [DOI] [PubMed] [Google Scholar]
• 12.Prall F, Nollau P, Neumaier M, Haubeck HD, Drzeniek Z, Helmchen U, Löning T, Wagener C. CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. J Histochem Cytochem. 1996;44:35–41. doi: 10.1177/44.1.8543780. [DOI] [PubMed] [Google Scholar]
• 13.Godfraind C, Langreth SG, Cardellichio CB, Knobler R, Coutelier JP, Dubois-Dalcq M, Holmes KV. Tissue and cellular distribution of an adhesion molecule in the carcinoembryonic antigen family that serves as a receptor for mouse hepatitis virus. Lab Invest. 1995;73:615–627. [PubMed] [Google Scholar]
• 14.Coutelier JP, Godfraind C, Dveksler GS, Wysocka M, Cardeliichio CB, Noël H, Holmes KV. B lymphocyte and macrophage expression of carcinoembryonic antigen-related adhesion molecules that serve as receptors for murine coronavirus. Eur J Immunol. 1994;24:1383–1390. doi: 10.1002/eji.1830240622. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 15.Möller MJ, Kammerer R, Grunert F, von Kleist S. Biliary glycoprotein (BGP) expression on T cells and on a natural-killer-cell sub-population. Int J Cancer. 1996;65:740–745. doi: 10.1002/(SICI)1097-0215(19960315)65:6<740::AID-IJC5>3.0.CO;2-Z. [DOI] [PubMed] [Google Scholar]
• 16.Daniels E, Letourneau S, Turbide C, Kuprina N, Rudinskaya T, Yazova AC, Holmes KV, Dveksler GS, Beauchemin N. Biliary glycoprotein 1 expression during embryogenesis: correlation with events of epithelial differentiation, mesenchymal-epithelial interactions, absorption, and myogenesis. Dev Dyn. 1996;206:272–290. doi: 10.1002/(SICI)1097-0177(199607)206:3<272::AID-AJA5>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
• 17.Sawa H, Ukita H, Fukuda M, Kamada H, Saito I, Öbrink B. Spatiotemporal expression of C-CAM in the rat placenta. J Histochem Cytochem. 1997;45:1021–1034. doi: 10.1177/002215549704500711. [DOI] [PubMed] [Google Scholar]
• 18.Sawa H, Kamada K, Sato H, Sendo S, Kondo A, Saito I, Edlund M, Öbrink B. C-CAM expression in the developing rat central nervous system. Dev Brain Res. 1994;78:35–43. doi: 10.1016/0165-3806(94)90006-x. [DOI] [PubMed] [Google Scholar]
• 19.Lüning C, Wroblewski J, Öbrink B, Hammarström L, Rozell B. C-CAM expression in odontogenesis and tooth eruption. Connect Tissue Res. 1995;32:201–207. doi: 10.3109/03008209509013724. [DOI] [PubMed] [Google Scholar]
• 20.Hixson DC, McEntire KD, Öbrink B. Alterations in the expression of a hepatocyte cell adhesion molecule by transplantable rat hepatocellular carcinomas. Cancer Res. 1985;45:3742–3749. [PubMed] [Google Scholar]
• 21.Kim J, Kaye FJ, Henslee JG, Shively JE, Park JG, Lai SL, Linnoila RI, Mulshine JL, Gazdar AF. Expression of carcinoembryonic antigen and related genes in lung and gastrointestinal cancers. Int J Cancer. 1992;52:718–725. doi: 10.1002/ijc.2910520509. [DOI] [PubMed] [Google Scholar]
• 22.Neumaier M, Paululat S, Chan A, Matthaes P, Wagener C. Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. Proc Natl Acad Sci USA. 1993;90:10744–10748. doi: 10.1073/pnas.90.22.10744. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 23.Rosenberg M, Nédellec P, Jothy S, Fleiszer D, Turbide C, Beauchemin N. The expression of mouse biliary glycoprotein, a carcinoembryonic antigen-related gene, is down-regulated in malignant mouse tissues. Cancer Res. 1993;53:4938–4945. [PubMed] [Google Scholar]
• 24.Thompson J, Zimmermann W, Nollau P, Neumaier M, Weber-Arden J, Schrewe H, Craig I, Willcocks T. CGM2, a member of the carcinoembryonic antigen gene family is down-regulated in colorectal carcinomas. J Biol Chem. 1994;269:32924–32931. [PubMed] [Google Scholar]
• 25.Ohwada A, Takahashi H, Nagaoka I, Kira S. Biliary glycoprotein mRNA expression is increased in primary lung cancer, especially in squamous cell carcinoma. Am J Respir Cell Mol Biol. 1994;11:214–220. doi: 10.1165/ajrcmb.11.2.8049082. [DOI] [PubMed] [Google Scholar]
• 26.Kleinerman DI, Troncoso P, Lin SH, Pisters LL, Sherwood ER, Brooks T, von Eschenbach AC, Hsieh JT. Consistent expression of an epithelial cell adhesion molecule (C-CAM) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor. Cancer Res. 1995;55:1215–1220. [PubMed] [Google Scholar]
• 27.Tanaka K, Hinoda Y, Takahashi H, Sakamoto H, Nakajima Y, Imai K. Decreased expression of biliary glycoprotein in hepatocellular carcinomas. Int J Cancer. 1997;74:15–19. doi: 10.1002/(sici)1097-0215(19970220)74:1<15::aid-ijc3>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
• 28.Oikawa S, Kuroki M, Matsuoka Y, Kosaki G, Nakazato H. Homotypic and heterotypic Ca++-independent cell adhesion activities of biliary glycoprotein, a member of carcinoembryonic antigen family, expressed on CHO cell surface. Biochem Biophys Res Commun. 1992;186:881–887. doi: 10.1016/0006-291x(92)90828-9. [DOI] [PubMed] [Google Scholar]
• 29.Wilkström K, Kjellström G, Öbrink B. Homophilic intercellular adhesion mediated by C-CAM is due to a domain 1—domain 1 reciprocal binding. Exp Cell Res. 1996;227:360–366. doi: 10.1006/excr.1996.0285. [DOI] [PubMed] [Google Scholar]
• 30.Zhou H, Fuks A, Alcaraz G, Bolling TJ, Stanners CP. Homophilic adhesion between Ig superfamily carcinoembryonic antigen molecules involves double reciprocal bonds. J Cell Biol. 1993;122:951–960. doi: 10.1083/jcb.122.4.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 31.Sippel CJ, Shen T, Perlmutter DH. Site-directed mutagenesis within an ectoplasmic ATPase consensus sequence abrogates the cell aggregating properties of the rat liver canalicular bile acid transporter/ecto-ATPase/cellCAM 105 and carcinoembryonic antigen. J Biol Chem. 1996;271:33095–33104. doi: 10.1074/jbc.271.51.33095. of special interest. [DOI] [PubMed] [Google Scholar]; This paper demonstrates that structural integrity of both the amino-terminal Ig domain and the cytoplasmic long domain of cell—cell adhesion molecule (C-CAM) is needed for adhesion as well as for ecto-ATPase activity.
• 32.Bates PA, Lou J, Sternberg MJE. A predicted three-dimensional structure for the carcinoembryonic antigen (CEA) FEBS Lett. 1992;301:207–214. doi: 10.1016/0014-5793(92)81249-l. [DOI] [PubMed] [Google Scholar]
• 33.Cheung PH, Culic O, Qiu Y, Earley K, Thompson N, Hixson DC, Lin SH. The cytoplasmic domain of C-CAM is required for C-CAM-mediated adhesion function: studies of a C-CAM transcript containing an unspliced intron. Biochem J. 1993;295:427–435. doi: 10.1042/bj2950427. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 34.Olsson H, Wikström K, Kjellström G, Öbrink B. Cell adhesion activity of the short cytoplasmic domain isoform of C-CAM (C-CAM2) in CHO cells. FEBS Lett. 1995;365:51–56. doi: 10.1016/0014-5793(95)00436-d. [DOI] [PubMed] [Google Scholar]
• 35.Lucka L, Cichocka I, Bäumler K, Bechler K, Reutter W. A short isoform of carcinoembryonic-antigen-related rat liver cell-cell adhesion molecule (C-CAM/gp 110) mediates intercellular adhesion. Eur J Biochem. 1995;234:527–535. doi: 10.1111/j.1432-1033.1995.527_b.x. [DOI] [PubMed] [Google Scholar]
• 36.Kuijpers TW, Hoogerwerf M, van der Laan LJW, Nagel G, van der Schoot CE, Grunert F, Roos D. CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells. J Cell Biol. 1992;118:457–466. doi: 10.1083/jcb.118.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 37.Stocks SC, Kerr MA, Haslett C, Dransfield I. CD66-dependent neutrophil activation: a possible mechanism for vascular selectin-mediated regulation of neutrophil adhesion. J Leukoc Biol. 1995;58:40–48. doi: 10.1002/jlb.58.1.40. [DOI] [PubMed] [Google Scholar]
• 38.Kuijpers TW, van der Schoot CE, Hoogerwerf M, Roos D. Cross-linking of the carcinoembryonic antigen-like glycoproteins CD66 and CD67 induces neutrophil aggregation. J Immunol. 1993;151:4934–4940. [PubMed] [Google Scholar]
• 39.Hashimoto S, Yamamura S, Shimono M. Morphometric analysis of the intercellular space and desmosomes of rat junctional epithelium. J Periodontal Res. 1986;21:510–520. doi: 10.1111/j.1600-0765.1986.tb01487.x. [DOI] [PubMed] [Google Scholar]
• 40.Mowery J, Hixson DC. Detection of cell-CAM 105 in the pericanalicular domain of the rat hepatocyte plasma membrane. Hepatology. 1991;13:47–56. [PubMed] [Google Scholar]
• 41.Baranov V, Yeung MW, Hammarström S. Expression of carcinoembryonic antigen and nonspecific cross-reacting 50-kDa antigen in human normal and cancerous colon mucosa: comparative ultrastructural study with monoclonal antibodies. Cancer Res. 1994;54:3305–3314. [PubMed] [Google Scholar]
• 42.Lin SH, Guidotti G. Cloning and expression of a cDNA coding for a rat liver plasma membrane ecto-ATPase. J Biol Chem. 1989;264:14408–14414. [PubMed] [Google Scholar]
• 43.Sippel CJ, Fallon RJ, Perlmutter DH. Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto-ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine 488 phosphorylation. J Biol Chem. 1994;269:19539–19545. [PubMed] [Google Scholar]
• 44.Stout JG, Strobel RS, Kirley TL. Properties of and proteins associated with the extracellular ATPase of chicken gizzard smooth muscle. A monoclonal antibody study. J Biol Chem. 1995;270:11845–11850. doi: 10.1074/jbc.270.20.11845. [DOI] [PubMed] [Google Scholar]
• 45.Becker A, Lucka L, Kilian C, Kannicht C, Reutter W. Characterization of the ATP-dependent taurocholate-carrier protein (gp110) of the hepatocyte canalicular membrane. Eur J Biochem. 1993;214:539–548. doi: 10.1111/j.1432-1033.1993.tb17952.x. [DOI] [PubMed] [Google Scholar]
• 46.Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci USA. 1991;88:10629–10633. doi: 10.1073/pnas.88.23.10629. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 47.Wong MH, Oelkers P, Craddock AL, Dawson PA. Expression cloning and characterization of the hamster ileal sodium-dependent bile acid transporter. J Biol Chem. 1994;269:1340–1347. [PubMed] [Google Scholar]
• 48.Formisano P, Najjar SM, Gross CN, Philippe N, Oriente F, Kern-Buell CL, Accili D, Gorden P. Receptor-mediated internalization of insulin. J Biol Chem. 1995;270:24073–24077. doi: 10.1074/jbc.270.41.24073. [DOI] [PubMed] [Google Scholar]
• 49.Leusch HG, Drzeniek Z, Markos-Pusztal Z, Wagener C. Binding of Escherichia coli and Salmonella strains to members of the carcinoembryonic antigen family: differential binding inhibition by aromatic α-glycosides of mannose. Infect Immun. 1991;59:2051–2057. doi: 10.1128/iai.59.6.2051-2057.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 50.Sauter SL, Rutherford SM, Wagener C, Shively JE, Hefta SA. Identification of the specific oligosaccharide sites recognized by type 1 fimbriae from Escherichia coli on nonspecific cross-reacting antigen, a CD66 cluster granulocyte glycoprotein. J Biol Chem. 1993;268:15510–15516. [PubMed] [Google Scholar]
• 51.Virji M, Watt SM, Barker S, Makepeace K, Doyonnas R. The N-domain of the human CD66a adhesion molecule is a target for Opa proteins of Neisseria meningitidis and Neisseria gonorrhoeae. Mol Microbiol. 1996;22:929–939. doi: 10.1046/j.1365-2958.1996.01548.x. [DOI] [PubMed] [Google Scholar]
• 52.Bos MP, Grunert F, Belland RJ. Differential recognition of members of the carcinoembryonic antigen family by Opa variants of Neisseria gonorrhoeae. Infect Immun. 1997;65:2353–2361. doi: 10.1128/iai.65.6.2353-2361.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 53.Dveksler GS, Dieffenbach CW, Cardellichio CB, McCuaig K, Pensiero MN, Jiang GS, Beauchemin N, Holmes KV. Several members of the mouse carcinoembryonic antigen-related glycoprotein family are functional receptors for the coronavirus mouse hepatitis virus-A59. J Virol. 1993;67:1–8. doi: 10.1128/jvi.67.1.1-8.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 54.Ohtsuka N, Yamada YK, Taguchi F. Difference in virus-binding activity of two distinct receptor proteins for mouse hepatitis virus. J Gen Virol. 1996;77:1683–1692. doi: 10.1099/0022-1317-77-8-1683. [DOI] [PubMed] [Google Scholar]
• 55.Rojas M, DeMarte L, Screaton RA, Stanners CP. Radical differences in functions of closely related members of the human carcinoembryonic antigen gene family. Cell Growth Differ. 1996;7:655–662. [PubMed] [Google Scholar]
• 56.Screaton RA, Penn LZ, Stanners CP. Carcinoembryonic antigen, a human tumor marker, cooperates with myc and bcl-2 in cellular transformation. J Cell Biol. 1997;137:939–952. doi: 10.1083/jcb.137.4.939. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 57.Stocks SC, Ruchaud-Sparagano MH, Kerr MA, Grunert F, Haslett C, Dransfield I. CD66: role in the regulation of neutrophil effector function. Int J Immunol. 1996;26:2924–2932. doi: 10.1002/eji.1830261218. of special interest. [DOI] [PubMed] [Google Scholar]; Using monoclonal antibodies it was demonstrated that antibody stimulation of cell—cell adhesion molecule (C-CAM) in human granulocytes caused activation of β2-integrin-mediated adhesion and a respiratory burst. Co-ligation of C-CAM, CGM6 and NCA had the same effect, but ligation of CGM6 or NCA alone did not trigger these responses. This indicates that the signaling effects are mediated by the transmembrane C-CAM.
• 58.Skubitz KM, Campbell KD, Skubitz APN. CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. J Leukoc Biol. 1996;60:106–117. doi: 10.1002/jlb.60.1.106. of special interest. [DOI] [PubMed] [Google Scholar]; Antibody ligation of C-CAM, CGM6, NCA or CGM1 in human granulocytes triggered β2-integrin-mediated adhesion to endothelial cells by a transient activation signal that required extracellular calcium.
• 59.Jantscheff P, Nagel G, Thompson J, von Kleist S, Embleton MJ, Price MR, Grunert F. A CD66a-specific, activation-dependent epitope detected by recombinant human single chain fragments (scFvs) on CHO transfectants and activated granulocytes. J Leukoc Biol. 1996;59:891–901. doi: 10.1002/jlb.59.6.891. [DOI] [PubMed] [Google Scholar]
• 60.Turbide C, Kunath T, Daniels E, Beauchemin N. Optimal ratios of biliary glycoprotein isoforms required for inhibition of colonic turmor cell growth. Cancer Res. 1997;57:2781–2788. of outstanding interest. [PubMed] [Google Scholar]; This is an important paper demonstrating that the long and the short isoforms of cell—cell adhesion molecule (C-CAM) cooperate in regulating tumor growth. It indicates that the signaling properties of the long isoform are modified by the short isoform.
• 61.Kunath T, Ordonez-Garcia C, Turbide C, Beauchemin N. Inhibition of colonic tumor cell growth by biliary glycoprotein. Oncogene. 1995;11:2375–2382. [PubMed] [Google Scholar]
• 62.Hsieh JT, Luo W, Song W, Wang Y, Kleinerman DI, Van NT, Lin SH. Tumor suppressive role of an androgen-regulated epithelial cell adhesion molecule (C-CAM) in prostate carcinoma cell revealed by sense and antisense approaches. Cancer Res. 1995;55:190–197. [PubMed] [Google Scholar]
• 63.Kleinerman DI, Dinney CPN, Zhang WW, Lin SH, Van NT, Hsieh JT. Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model. Cancer Res. 1996;56:3431–3435. of special interest. [PubMed] [Google Scholar]; See annotation [64].
• 64.Luo W, Wood CG, Earley K, Hung MC, Lin SH. Suppression of tumorigenicity of breast cancer cells by an epithelial cell adhesion molecule (C-CAM1): the adhesion and growth suppression are mediated by different domains. Oncogene. 1997;14:1697–1704. doi: 10.1038/sj.onc.1200999. of special interest. [DOI] [PubMed] [Google Scholar]; These two papers [63,64] demonstrate that the long isoform of cell—cell adhesion molecule (C-CAM) can inhibit tumor growth of several different types of carcinomas. It is also demonstrated that the cytoplasmic domain, but not the amino-terminal Ig domain, is needed for tumor inhibition.
• 65.Kleinerman DI, Zhang WW, Lin SH, Van NT, von Eschenbach AC, Hsieh JT. Application of a tumor suppressor (C-CAM1)-expressing recombinant adenovirus in androgen-independent human prostate cancer therapy: a preclinical study. Cancer Res. 1995;55:2831–2836. [PubMed] [Google Scholar]
• 66.Baum O, Troll S, Hixson DC. The long and the short isoform of cell-CAM 105 show variant-specific modifications in adult rat organs. Biochem Biophys Res Commun. 1996;227:775–781. doi: 10.1006/bbrc.1996.1584. [DOI] [PubMed] [Google Scholar]
• 67.Hunter I, Lindh M, Öbrink B. Differential regulation of C-CAM isoforms in epithelial cells. J Cell Sci. 1994;107:1205–1216. doi: 10.1242/jcs.107.5.1205. [DOI] [PubMed] [Google Scholar]
• 68.Margolis RN, Schell MJ, Taylor SI, Hubbard AL. Hepatocyte plasma membrane ecto-ATPase (pp120/HA4) is a substrate for tyrosine kinase activity of the insulin receptor. Biochem Biophys Res Commun. 1991;166:562–566. doi: 10.1016/0006-291x(90)90845-e. [DOI] [PubMed] [Google Scholar]
• 69.Brümmer J, Neumaier M, Göpfert C, Wagener C. Association of pp60c-src with biliary glycoprotein (CD66a), an adhesion molecule of the carcinoembryonic antigen family downregulated in colorectal carcinomas. Oncogene. 1995;11:1649–1655. [PubMed] [Google Scholar]
• 70.Skubitz KM, Campbell KD, Ahmed K, Skubitz APN. CD66 family members are associated with tyrosine kinase activity in human neutrophils. J Immunol. 1995;155:5382–5390. [PubMed] [Google Scholar]
• 71.Beauchemin N, Kunath T, Robitaille J, Chow B, Turbide C, Daniels E, Veillette A. Association of biliary glycoprotein with protein tyrosine phosphatase SHP-1 in malignant colon epithelial cells. Oncogene. 1997;14:783–790. doi: 10.1038/sj.onc.1200888. of special interest. [DOI] [PubMed] [Google Scholar]; This paper is the first demonstration that a protein tyrosine phosphatase that is involved in negative regulation of hematopoietic cells can be recruited by the long cell—cell adhesion molecule (C-CAM) isoform in an epithelial cell.
• 72.Daeron M, Latour S, Malbec O, Espinosa E, Pina P, Pasmans S, Fridman WH. The same tyrosine-based inhibition motif, in the intra-cytoplasmic domain of FcγRIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation. Immunity. 1995;3:635–646. doi: 10.1016/1074-7613(95)90134-5. [DOI] [PubMed] [Google Scholar]
• 73.Burshtyn DN, Scharenberg AM, Wagtman N, Rajagopalan S, Berrada K, Yi T, Kinet JP, Long EO. Recruitment of tyrosine phosphatase HCP by the killer cell inhibitory receptor. Immunity. 1996;4:77–85. doi: 10.1016/s1074-7613(00)80300-3. of special interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; This paper demonstrates that the protein tyrosine phosphatase SHP-1 is recruited by the natural killer cell inhibitory receptor when it becomes tyrosine phosphorylated. It was also shown that an inactivated mutated phosphatase prevented the receptor-mediated inhibition of target cell lysis.
• 74.Edlund M, Blikstad I, Öbrink B. Calmodulin binds to specific sequences in the cytoplasmic domain of C-CAM and downregulates C-CAM self-association. J Biol Chem. 1996;271:1393–1399. doi: 10.1074/jbc.271.3.1393. of special interest. [DOI] [PubMed] [Google Scholar]; In this paper, the calmodulin-binding sequences in cell—cell adhesion molecule (C-CAM) were identified. It was also demonstrated that calcium-mediated binding of calmodulin to C-CAM inhibited C-CAM homophilic binding.
• 75.Hunter I, Sawa H, Edlund M, Öbrink B. Evidence for regulated dimerization of cell-cell adhesion molecule (C-CAM) in epithelial cells. Biochem J. 1996;320:847–853. doi: 10.1042/bj3200847. of special interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; The authors of this paper demonstrated that both the long and the short isoforms of cell—cell adhesion molecule (C-CAM) can form dimers. The dimers were dissociated by calcium-induced binding of calmodulin.
• 76.Fujioka Y, Matozaki T, Noguchi T, Iwamatsu A, Yamao T, Takahashi N, Tsuda M, Takada T, Kasuga M. A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol Cell Biol. 1996;16:6887–6899. doi: 10.1128/mcb.16.12.6887. of outstanding interest. [DOI] [PMC free article] [PubMed] [Google Scholar]; See annotation [77].
• 77.Kharitonenkov A, Chen Z, Sures I, Wang H, Schilling J, Ullrich A. A family of proteins that inhibit signalling through tyrosine kinase receptors. Nature. 1997;386:181–186. doi: 10.1038/386181a0. of outstanding interest. [DOI] [PubMed] [Google Scholar]; The authors of this paper, together with those of [76], identified a new family of signal-regulatory proteins that can recruit protein tyrosine phosphatases when they become tyrosine phosphorylated in their cytoplasmic domains. This recruitment leads to inhibition of cellular proliferation.
• 78.DeLisser HM, Chilkotowsky J, Yan HC, Daise ML, Buck CA, Abelda SM. Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties. J Cell Biol. 1994;124:195–203. doi: 10.1083/jcb.124.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
• 79.Jackson DE, Ward CM, Wang R, Newman PJ. The protein-tyrosine phosphatase SHP-2 binds platelet/endothelial cell adhesion molecule-1 (PECAM-1) and forms a distinct signaling complex during platelet aggregation. J Biol Chem. 1997;272:6986–6993. doi: 10.1074/jbc.272.11.6986. of special interest. [DOI] [PubMed] [Google Scholar]; Platelet aggregation leads to tyrosine phosphorylation of platelet/endothelial cell adhesion molecule-1 and recruitment of the protein tyrosine phosphatase SHP-2.