TY - JOUR
T1 - The SH3 domain-binding T cell tyrosyl phosphoprotein p120. Demonstration of its identity with the c-cbl protooncogene product and in vivo complexes with Fyn, Grb2, and phosphatidylinositol 3-kinase
AU - Fukazawa, T.
AU - Reedquist, K. A.
AU - Trub, T.
AU - Soltoff, S.
AU - Panchamoorthy, G.
AU - Druker, B.
AU - Cantley, L.
AU - Shoelson, S. E.
AU - Band, H.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1995
Y1 - 1995
N2 - Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain- binding protein that is tyrosine phosphorylated rapidly after T cell receptor triggering. Here, we used direct protein purification, amino acid sequence analysis, reactivity with antibodies, and two-dimensional gel analyses to identify p120 as the human c-cbl protooncogene product. We demonstrate in vivo complexes of p120(cbl) with Fyn tyrosine kinase, the adaptor protein Grb2, and the p85 subunit of phosphatidylinositol (PI) 3-kinase. The association of p120(cbl) with Fyn and the p85 subunit of PI 3-kinase (together with PI 3-kinase activity) was markedly increased by T cell activation, consistent with in vitro binding of p120(cbl) to their SH2 as well as SH3 domains. In contrast, a large fraction of p120(cbl) was associated with Grb2 prior to activation, and this association did not change upon T cell activation. In vitro, p120(cbl) interacted with Grb2 exclusively through its SH3 domains. These results demonstrate a novel Grb2-p12(cbl) signaling complex in T cells, distinct from the previously analyzed Grb2-Sos complex. The association of p120(cbl) with ubiquitous signaling proteins strongly suggests a general signal transducing function for this enigmatic protooncogene with established leukemogenic potential but unknown physiological function.
AB - Previously, we have identified p120 as a Fyn/Lck SH3 and SH2 domain- binding protein that is tyrosine phosphorylated rapidly after T cell receptor triggering. Here, we used direct protein purification, amino acid sequence analysis, reactivity with antibodies, and two-dimensional gel analyses to identify p120 as the human c-cbl protooncogene product. We demonstrate in vivo complexes of p120(cbl) with Fyn tyrosine kinase, the adaptor protein Grb2, and the p85 subunit of phosphatidylinositol (PI) 3-kinase. The association of p120(cbl) with Fyn and the p85 subunit of PI 3-kinase (together with PI 3-kinase activity) was markedly increased by T cell activation, consistent with in vitro binding of p120(cbl) to their SH2 as well as SH3 domains. In contrast, a large fraction of p120(cbl) was associated with Grb2 prior to activation, and this association did not change upon T cell activation. In vitro, p120(cbl) interacted with Grb2 exclusively through its SH3 domains. These results demonstrate a novel Grb2-p12(cbl) signaling complex in T cells, distinct from the previously analyzed Grb2-Sos complex. The association of p120(cbl) with ubiquitous signaling proteins strongly suggests a general signal transducing function for this enigmatic protooncogene with established leukemogenic potential but unknown physiological function.
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U2 - 10.1074/jbc.270.32.19141
DO - 10.1074/jbc.270.32.19141
M3 - Article
C2 - 7642581
AN - SCOPUS:0029051695
VL - 270
SP - 19141
EP - 19150
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 32
ER -