Engagement of the vitronectin receptor (alpha V beta 3) on murine T cells stimulates tyrosine phosphorylation of a 115-kDa protein.
The murine vitronectin receptor (VNR, alpha V beta 3) is expressed on T cell hybridomas expressing both the alpha beta and the gamma delta TCR as well as on TCR-alpha beta cells activated for prolonged periods of time by mitogens or alloantigens. The VNR functions as a costimulatory molecule for the activation of a subset of gamma delta T cells that express the V gamma 1.1 C gamma 4 V delta 6 TCR and that may recognize a ubiquitously expressed autoantigen. To characterize further some of the signal transduction parameters observed after engagement of the VNR in stimulated T lymphocytes, we have examined the effect of ligation of the VNR by RGDS-containing proteins on the pattern of protein phosphorylation. We demonstrate the appearance of a 115-kDa, tyrosine-phosphorylated protein (pp115) after engagement of the VNR with its ligand, RGDS. pp115 was shown to be immunologically distinct from focal adhesion kinase, did not possess inherent kinase activity, and may represent an as yet unidentified substrate in the integrin signal transduction pathway. Although induction of pp115 was independent of TCR expression, because it was seen in the TG40 hybridoma, which expresses neither the alpha beta nor the gamma delta TCR, pp115 could also be induced by cross-linking of the TCR in a murine TCR gamma delta hybridoma in the absence of any extracellular matrix proteins. This result raises the possibility that induction of pp115 is a common biochemical step in signal transduction by both the TCR and the VNR.
Brando
C
C
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Shevach
E M
EM
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D005353:Fibronectins / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D016024:Receptors, Cytoadhesin / Q000378:metabolism*; D019030:Receptors, Vitronectin; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D005353:Fibronectins; D016023:Integrins; D009842:Oligopeptides; D011506:Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D014443:Tyrosine; C046617:arginyl-glycyl-aspartyl-serine; D011494:Protein Kinases