Tsygankov A Y, Mahajan S, Fincke J E, Bolen J B
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
J Biol Chem. 1996 Oct 25;271(43):27130-7. doi: 10.1074/jbc.271.43.27130.
Fyn is a Src family protein-tyrosine kinase functionally associated with the T-cell antigen receptor (TcR)/CD3 receptor complex. We have demonstrated earlier that the TcR/CD3-induced activation of Fyn results in tyrosine phosphorylation of several Fyn-associated proteins, including a protein of 116 kDa. In this report, we identify the Fyn-associated 116-kDa phosphoprotein (p116) as c-Cbl. The identity of p116 has been demonstrated by its specific reactivity with anti-Cbl and similarity of phosphopeptides generated by V8 proteolysis of phospho-Cbl and p116. We demonstrate here that the association of Fyn and c-Cbl is direct and does not require the presence of other proteins. We also demonstrate that Fyn is the Src family kinase that preferentially interacts with c-Cbl in T cells. The fraction of c-Cbl capable of coprecipitating with Fyn is increased by TcR/CD3 ligation. This increase is likely due to the involvement of Fyn SH2 in the interactions between Fyn and tyrosine-phosphorylated c-Cbl.
Fyn是一种与T细胞抗原受体（TcR）/CD3受体复合物功能相关的Src家族蛋白酪氨酸激酶。我们之前已经证明，TcR/CD3诱导的Fyn激活会导致几种与Fyn相关的蛋白发生酪氨酸磷酸化，包括一种116 kDa的蛋白。在本报告中，我们鉴定出与Fyn相关的116 kDa磷蛋白（p116）为c-Cbl。p116的身份已通过其与抗Cbl的特异性反应以及磷酸化Cbl和p116经V8蛋白酶解产生的磷酸肽的相似性得以证明。我们在此证明Fyn与c-Cbl的结合是直接的，不需要其他蛋白的存在。我们还证明Fyn是在T细胞中优先与c-Cbl相互作用的Src家族激酶。TcR/CD3连接会增加能够与Fyn共沉淀的c-Cbl的比例。这种增加可能是由于Fyn的SH2参与了Fyn与酪氨酸磷酸化的c-Cbl之间的相互作用。
