Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 May;150(5):1523–1530.

Platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) tyrosine phosphorylation state changes during vasculogenesis in the murine conceptus.

E Pinter 1, M Barreuther 1, T Lu 1, B A Imhof 1, J A Madri 1
PMCID: PMC1858227  PMID: 9137078

Abstract

Vasculogenesis, the differentiation of mesodermal cells to angioblasts and the subsequent formation of blood islands and blood vessels by angioblasts in the conceptus, is a dynamic process modulated, in part, by cell-extracellular matrix and cell-cell interactions in the presence of a variety of growth factors and morphogens. In this report we demonstrate differential tyrosine phosphorylation of platelet-endothelial cell adhesion molecule-1 (PECAM-1) during the formation of blood islands and vessels from clusters of extraembryonic and embryonic angioblasts in the murine conceptus. In addition, we identify the phosphorylation of a particular tyrosine residue in the PECAM-1 cytoplasmic domain, Tyr686, which has the potential of mediating binding to Src homology 2 domain-containing proteins, affecting PECAM-1 cellular localization and endothelial cell migration.

Full text

PDF
1523

Images in this article

1526Figure 1
on p.1526
1527Figure 2
on p.1527
1527Figure 3
on p.1527

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M., Muller W. A., Buck C. A., Newman P. J. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule. J Cell Biol. 1991 Sep;114(5):1059–1068. doi: 10.1083/jcb.114.5.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldwin H. S. Early embryonic vascular development. Cardiovasc Res. 1996 Feb;31(Spec No):E34–E45. [PubMed] [Google Scholar]
  3. Baldwin H. S., Shen H. M., Yan H. C., DeLisser H. M., Chung A., Mickanin C., Trask T., Kirschbaum N. E., Newman P. J., Albelda S. M. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development. Development. 1994 Sep;120(9):2539–2553. doi: 10.1242/dev.120.9.2539. [DOI] [PubMed] [Google Scholar]
  4. Bangalore L., Tanner A. J., Laudano A. P., Stern D. F. Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11637–11641. doi: 10.1073/pnas.89.23.11637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berman M. E., Muller W. A. Ligation of platelet/endothelial cell adhesion molecule 1 (PECAM-1/CD31) on monocytes and neutrophils increases binding capacity of leukocyte CR3 (CD11b/CD18). J Immunol. 1995 Jan 1;154(1):299–307. [PubMed] [Google Scholar]
  6. Bogen S., Pak J., Garifallou M., Deng X., Muller W. A. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med. 1994 Mar 1;179(3):1059–1064. doi: 10.1084/jem.179.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Breier G., Breviario F., Caveda L., Berthier R., Schnürch H., Gotsch U., Vestweber D., Risau W., Dejana E. Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Blood. 1996 Jan 15;87(2):630–641. [PubMed] [Google Scholar]
  8. DeLisser H. M., Chilkotowsky J., Yan H. C., Daise M. L., Buck C. A., Albelda S. M. 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 Jan;124(1-2):195–203. doi: 10.1083/jcb.124.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dejana E. Endothelial adherens junctions: implications in the control of vascular permeability and angiogenesis. J Clin Invest. 1996 Nov 1;98(9):1949–1953. doi: 10.1172/JCI118997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fawcett J., Buckley C., Holness C. L., Bird I. N., Spragg J. H., Saunders J., Harris A., Simmons D. L. Mapping the homotypic binding sites in CD31 and the role of CD31 adhesion in the formation of interendothelial cell contacts. J Cell Biol. 1995 Mar;128(6):1229–1241. doi: 10.1083/jcb.128.6.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. George E. L., Georges-Labouesse E. N., Patel-King R. S., Rayburn H., Hynes R. O. Defects in mesoderm, neural tube and vascular development in mouse embryos lacking fibronectin. Development. 1993 Dec;119(4):1079–1091. doi: 10.1242/dev.119.4.1079. [DOI] [PubMed] [Google Scholar]
  12. Gumbiner B. M. Cell adhesion: the molecular basis of tissue architecture and morphogenesis. Cell. 1996 Feb 9;84(3):345–357. doi: 10.1016/s0092-8674(00)81279-9. [DOI] [PubMed] [Google Scholar]
  13. Johnson L. N., Noble M. E., Owen D. J. Active and inactive protein kinases: structural basis for regulation. Cell. 1996 Apr 19;85(2):149–158. doi: 10.1016/s0092-8674(00)81092-2. [DOI] [PubMed] [Google Scholar]
  14. Lastres P., Almendro N., Bellón T., López-Guerrero J. A., Eritja R., Bernabéu C. Functional regulation of platelet/endothelial cell adhesion molecule-1 by TGF-beta 1 in promonocytic U-937 cells. J Immunol. 1994 Nov 1;153(9):4206–4218. [PubMed] [Google Scholar]
  15. Leavesley D. I., Oliver J. M., Swart B. W., Berndt M. C., Haylock D. N., Simmons P. J. Signals from platelet/endothelial cell adhesion molecule enhance the adhesive activity of the very late antigen-4 integrin of human CD34+ hemopoietic progenitor cells. J Immunol. 1994 Nov 15;153(10):4673–4683. [PubMed] [Google Scholar]
  16. Lu T. T., Yan L. G., Madri J. A. Integrin engagement mediates tyrosine dephosphorylation on platelet-endothelial cell adhesion molecule 1. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11808–11813. doi: 10.1073/pnas.93.21.11808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Madri J. A., Bell L., Merwin J. R. Modulation of vascular cell behavior by transforming growth factors beta. Mol Reprod Dev. 1992 Jun;32(2):121–126. doi: 10.1002/mrd.1080320207. [DOI] [PubMed] [Google Scholar]
  18. Madri J. A., Pratt B. M., Tucker A. M. Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix. J Cell Biol. 1988 Apr;106(4):1375–1384. doi: 10.1083/jcb.106.4.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Modderman P. W., von dem Borne A. E., Sonnenberg A. Tyrosine phosphorylation of P-selectin in intact platelets and in a disulphide-linked complex with immunoprecipitated pp60c-src. Biochem J. 1994 May 1;299(Pt 3):613–621. doi: 10.1042/bj2990613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Newman P. J., Berndt M. C., Gorski J., White G. C., 2nd, Lyman S., Paddock C., Muller W. A. PECAM-1 (CD31) cloning and relation to adhesion molecules of the immunoglobulin gene superfamily. Science. 1990 Mar 9;247(4947):1219–1222. doi: 10.1126/science.1690453. [DOI] [PubMed] [Google Scholar]
  21. Newman P. J., Hillery C. A., Albrecht R., Parise L. V., Berndt M. C., Mazurov A. V., Dunlop L. C., Zhang J., Rittenhouse S. E. Activation-dependent changes in human platelet PECAM-1: phosphorylation, cytoskeletal association, and surface membrane redistribution. J Cell Biol. 1992 Oct;119(1):239–246. doi: 10.1083/jcb.119.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pawson T. SH2 and SH3 domains in signal transduction. Adv Cancer Res. 1994;64:87–110. doi: 10.1016/s0065-230x(08)60835-0. [DOI] [PubMed] [Google Scholar]
  23. Piali L., Albelda S. M., Baldwin H. S., Hammel P., Gisler R. H., Imhof B. A. Murine platelet endothelial cell adhesion molecule (PECAM-1)/CD31 modulates beta 2 integrins on lymphokine-activated killer cells. Eur J Immunol. 1993 Oct;23(10):2464–2471. doi: 10.1002/eji.1830231013. [DOI] [PubMed] [Google Scholar]
  24. Piali L., Hammel P., Uherek C., Bachmann F., Gisler R. H., Dunon D., Imhof B. A. CD31/PECAM-1 is a ligand for alpha v beta 3 integrin involved in adhesion of leukocytes to endothelium. J Cell Biol. 1995 Jul;130(2):451–460. doi: 10.1083/jcb.130.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pinter E., Reece E. A., Leranth C. Z., Sanyal M. K., Hobbins J. C., Mahoney M. J., Naftolin F. Yolk sac failure in embryopathy due to hyperglycemia: ultrastructural analysis of yolk sac differentiation associated with embryopathy in rat conceptuses under hyperglycemic conditions. Teratology. 1986 Feb;33(1):73–84. doi: 10.1002/tera.1420330110. [DOI] [PubMed] [Google Scholar]
  26. Polverini P. J. Cellular adhesion molecules. Newly identified mediators of angiogenesis. Am J Pathol. 1996 Apr;148(4):1023–1029. [PMC free article] [PubMed] [Google Scholar]
  27. Risau W., Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995;11:73–91. doi: 10.1146/annurev.cb.11.110195.000445. [DOI] [PubMed] [Google Scholar]
  28. Schimmenti L. A., Yan H. C., Madri J. A., Albelda S. M. Platelet endothelial cell adhesion molecule, PECAM-1, modulates cell migration. J Cell Physiol. 1992 Nov;153(2):417–428. doi: 10.1002/jcp.1041530222. [DOI] [PubMed] [Google Scholar]
  29. Skubitz K. M., Goueli S. A. CD31 (PECAM-1), CDw32 (Fc gamma RII), and anti-HLA class I monoclonal antibodies recognize phosphotyrosine-containing proteins on the surface of human neutrophils. J Immunol. 1994 Jun 15;152(12):5902–5911. [PubMed] [Google Scholar]
  30. Sun Q. H., DeLisser H. M., Zukowski M. M., Paddock C., Albelda S. M., Newman P. J. Individually distinct Ig homology domains in PECAM-1 regulate homophilic binding and modulate receptor affinity. J Biol Chem. 1996 May 10;271(19):11090–11098. doi: 10.1074/jbc.271.19.11090. [DOI] [PubMed] [Google Scholar]
  31. Tanaka Y., Albelda S. M., Horgan K. J., van Seventer G. A., Shimizu Y., Newman W., Hallam J., Newman P. J., Buck C. A., Shaw S. CD31 expressed on distinctive T cell subsets is a preferential amplifier of beta 1 integrin-mediated adhesion. J Exp Med. 1992 Jul 1;176(1):245–253. doi: 10.1084/jem.176.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Vecchi A., Garlanda C., Lampugnani M. G., Resnati M., Matteucci C., Stoppacciaro A., Schnurch H., Risau W., Ruco L., Mantovani A. Monoclonal antibodies specific for endothelial cells of mouse blood vessels. Their application in the identification of adult and embryonic endothelium. Eur J Cell Biol. 1994 Apr;63(2):247–254. [PubMed] [Google Scholar]
  33. Yang J. T., Rayburn H., Hynes R. O. Embryonic mesodermal defects in alpha 5 integrin-deficient mice. Development. 1993 Dec;119(4):1093–1105. doi: 10.1242/dev.119.4.1093. [DOI] [PubMed] [Google Scholar]
  34. Zehnder J. L., Hirai K., Shatsky M., McGregor J. L., Levitt L. J., Leung L. L. The cell adhesion molecule CD31 is phosphorylated after cell activation. Down-regulation of CD31 in activated T lymphocytes. J Biol Chem. 1992 Mar 15;267(8):5243–5249. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES