Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase
Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase
复制标题
DOI：
10.1074/jbc.m101219200
复制
发表时间：
2001-06-22
影响因子：
4.8
通讯作者：
Sefton, BM
中科院分区：
文献类型：
--
作者：
Chiang, GG;Sefton, BM
蛋白酪氨酸磷酸酶SHP-1已被证明是造血细胞中多种信号通路的负调节因子。在这项研究中，我们证明当SHP-1在非淋巴样细胞中短暂共表达时，SHP-1会使淋巴细胞特异性Src家族激酶Lck的tyr394位点去磷酸化。我们还证明了GST-SHP-1融合蛋白在体外特异性地使Lck的tyr394去磷酸化。由于Tyr-394的磷酸化激活了Lck， SHP-1特异性地使该位点去磷酸化这一事实表明SHP-1是Lck的负调节因子。SHP-1失活Lck的失败可能导致在母鼠中观察到的一些淋巴异常。
The protein-tyrosine phosphatase SHP-1 has been shown to be a negative regulator of multiple signaling pathways in hematopoietic cells. In this study, we demonstrate that SHP-1 dephosphorylates the lymphoid-specific Src family kinase Lck at Tyr-394 when both are transiently co-expressed in nonlymphoid cells. We also demonstrate that a GST-SHP-1 fusion protein specifically dephosphorylates Lck at Tyr-394 in vitro. Because phosphorylation of Tyr-394 activates Lck, the fact that SHP-1 specifically dephosphorylates this site suggests that SHP-1 is a negative regulator of Lck. The failure of SHP-1 to inactivate Lck may contribute to some of the lymphoid abnormalities observed in motheaten mice.