Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation
Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl dephosphorylation
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DOI：
10.1016/s1097-2765(00)00138-6
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发表时间：
2000-12-01
期刊：
影响因子：
16
通讯作者：
Goff, SP
中科院分区：
文献类型：
--
作者：
Cong, F;Spencer, S;Goff, SP
对c-Abl相互作用蛋白的搜索导致了PSTPIP1的回收，PSTPIP1最初被鉴定为害虫类型蛋白酪氨酸磷酸酶(PTP)的结合蛋白。在Abl缺失的成纤维细胞中，PSTPIP1被c-Abl磷酸化，生长因子诱导的PSTPIP1磷酸化被抑制。PSTPIP1能够将c-Abl桥接到害虫类型的PTPs上。一些实验表明，PEST类型的PTPs负性调节c-Abl的活性：在PTP-PEST缺陷的细胞中，c-Abl过度磷酸化；PSTPIP1突变体过表达破坏c-Abl-PSTPIP1-PEST类型的PTP三元复合体，增加c-Abl的磷酸化酪氨酸含量；在PTP-PEST缺陷的细胞中，PDGF诱导的c-Abl激酶激活时间延长。PEST类型的PTP使c-Abl去磷酸化是调节c-Abl活性的一种新机制。
A search for c-Abl interacting proteins resulted in the recovery of PSTPIP1, originally identified as a binding protein of the PEST-type protein tyrosine phosphatases (PTP). PSTPIP1 was phosphorylated by c-Abl, and growth factor-induced PSTPIP1 phosphorylation was diminished in Abl null fibroblasts. PSTPIP1 was able to bridge c-Abl to the PEST-type PTPs. Several experiments suggest that the PEST-type PTPs negatively regulate c-Abl activity: c-Abl was hyperphosphorylated in PTP-PEST-deficient cells; disruption of the c-Abl-PSTPIP1-PEST-type PTP ternary complex by overexpression of PSTPIP1 mutants increased c-Abl phosphotyrosine content; and PDGF-induced c-Abl kinase activation was prolonged in PTP-PEST-deficient cells. Dephosphorylation of c-Abl by PEST-type PTP represents a novel mechanism by which c-Abl activity is regulated.