TY - JOUR
T1 - The protein tyrosine kinase ZAP-70 can associate with the SH2 domain of proto-Vav
AU - Katzav, Shulamit
AU - Sutherland, Mary
AU - Packham, Graham
AU - Yi, Taolin
AU - Weiss, Arthur
PY - 1994/12/23
Y1 - 1994/12/23
N2 - Stimulation of the T cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including the vav proto- oncogene product. We now report the detection of several phosphotyrosine proteins (80, 74, and 70 kDa) from TCR-stimulated T cells that bind to the Src homology 2 (SH2) domain of proto-Vav (Vav-SH2) and co-immunoprecipitate with the proto-Vav product. Their binding to Vav-SH2 differs from that observed with SH2 domains from other proteins. None of the Vav-SH2-associated phosphoproteins bind to either of the Src homology 3 (SH3) domains of proto- Vav or to mutant Vav-SH2 proteins. The association of the phosphoproteins with Vav-SH2 requires induction of tyrosine phosphorylation of cellular proteins since proteins from lysates of herbimycin A-treated TCR-activated T cells fail to associate with Vav-SH2. Among the proteins from T cells that co-immunoprecipitate with the proto-Vav product and bind to its SH2 domain, specific antibodies identified the 70-kDa tyrosine phosphoprotein as ZAP-70, a protein tyrosine kinase (PTK) involved in TCR signal transduction. Binding of this PTK to Vav-SH2 is inhibited by a ZAP-70-specific synthetic tyrosine phosphopeptide. We suggest that ZAP-70 may function as a PTK for proto-Vav.
AB - Stimulation of the T cell antigen receptor (TCR) leads to tyrosine phosphorylation of a number of cellular proteins, including the vav proto- oncogene product. We now report the detection of several phosphotyrosine proteins (80, 74, and 70 kDa) from TCR-stimulated T cells that bind to the Src homology 2 (SH2) domain of proto-Vav (Vav-SH2) and co-immunoprecipitate with the proto-Vav product. Their binding to Vav-SH2 differs from that observed with SH2 domains from other proteins. None of the Vav-SH2-associated phosphoproteins bind to either of the Src homology 3 (SH3) domains of proto- Vav or to mutant Vav-SH2 proteins. The association of the phosphoproteins with Vav-SH2 requires induction of tyrosine phosphorylation of cellular proteins since proteins from lysates of herbimycin A-treated TCR-activated T cells fail to associate with Vav-SH2. Among the proteins from T cells that co-immunoprecipitate with the proto-Vav product and bind to its SH2 domain, specific antibodies identified the 70-kDa tyrosine phosphoprotein as ZAP-70, a protein tyrosine kinase (PTK) involved in TCR signal transduction. Binding of this PTK to Vav-SH2 is inhibited by a ZAP-70-specific synthetic tyrosine phosphopeptide. We suggest that ZAP-70 may function as a PTK for proto-Vav.
UR - https://www.scopus.com/pages/publications/0028595695
U2 - 10.1016/s0021-9258(18)31673-9
DO - 10.1016/s0021-9258(18)31673-9
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 7798261
AN - SCOPUS:0028595695
SN - 0021-9258
VL - 269
SP - 32579
EP - 32585
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 51
ER -