CD2 antigen mediated activation of the guanine nucleotide binding proteins p21ras in human T lymphocytes.
T cell stimulation via the TCR complex (TCR/CD3 complex) results in activation of the guanine nucleotide binding proteins encoded by the ras protooncogenes (p21ras). In the present study we show that the activation state of p21ras in T lymphocytes can also be controlled by triggering of the CD2 Ag. The activation state of p21ras is controlled by GTP levels on p21ras. In T cells stimulation of protein kinase C is able to induce an accumulation of "active" p21ras-GTP complexes due to an inhibitory effect of protein kinase C stimulation on the intrinsic GTPase activity of p21ras. The regulatory effect of protein kinase C on p21ras GTPase activity appears to be mediated via regulation of GAP, the GTPase activating protein of p21ras. In the present report, we demonstrate that the TCR/CD3 complex and the CD2 Ag control the accumulation of p21ras-GTP complexes via a regulatory effect on p21ras GTPase activity. The TCR/CD3 complex and CD2 Ag are also able to control the cellular activity of GAP. These data demonstrate that p21ras is part of the signal transduction responses controlled by the CD2 Ag, and reveal that the TCR/CD3 complex and CD2 Ag control the activation state of p21ras via a similar mechanism.
Lymphocyte Activation Laboratory, Imperial Cancer Research Funds, London, UK.
J D
JD
Graves
J
J
Downward
S
S
Rayter
P
P
Warne
A L
AL
Tutt
M
M
Glennie
D A
DA
Cantrell
D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D020558:GTP Phosphohydrolases / Q000032:analysis; D019204:GTP-Binding Proteins / Q000502:physiology*; D020690:GTPase-Activating Proteins; D006801:Humans; D008213:Lymphocyte Activation; D011493:Protein Kinase C / Q000502:physiology; D011506:Proteins / Q000494:pharmacology; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D020703:ras GTPase-Activating Proteins
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D020690:GTPase-Activating Proteins; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D020703:ras GTPase-Activating Proteins; D011493:Protein Kinase C; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)