Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation
Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation
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DOI：
10.1038/sj.onc.1202411
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发表时间：
1999-02-04
期刊：
影响因子：
8
通讯作者：
Liu, YC
中科院分区：
文献类型：
--
作者：
Elly, C;Witte, S;Liu, YC
Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated, In heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both Syk(Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells, A Tyr-316 Chi-binding site in Syk was required for the association with and for the maximal tyrosine phosphorylation of Cbl-b, Mutation at a loss-of-function site (Gly-298) in Cbl-b-N disrupts its interaction with Syk, Cbl-b constitutively binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and the Crk-L-binding regions were mapped to the C-terminus of Cbl-b, The Crk-L-binding sites were further determined to be (YDVP)-D-655 and (YKIP)-K-709, With th, latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways.
