PDGF RECEPTOR AS A SPECIFIC IN-VIVO TARGET FOR LOW M(R) PHOSPHOTYROSINE PROTEIN PHOSPHATASE
PDGF RECEPTOR AS A SPECIFIC IN-VIVO TARGET FOR LOW M(R) PHOSPHOTYROSINE PROTEIN PHOSPHATASE
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DOI：
10.1016/0014-5793(95)00947-8
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发表时间：
1995-09-18
期刊：
影响因子：
3.5
通讯作者：
RAMPONI, G
中科院分区：
文献类型：
--
作者：
CHIARUGI, P;CIRRI, P;RAMPONI, G
低M（r）磷酸酪氨酸蛋白磷酸酶（Low M（r）phosphotyrosine protein phosphatase，LMW-PTP）是一种广泛存在于真核细胞中的18 kDa胞浆酶，催化磷酸酪氨酸残基的水解，在正常细胞和转化细胞中过表达抑制细胞增殖。其涉及活性位点标记序列C（12）XXXXXR（18），这是所有PTP家族成员的主要特征。为了鉴定LMW-PTP底物，我们在NIH-3 T3细胞中表达了催化惰性的Cys（12）至Ser磷酸酶突变体，其保留了其底物结合能力，突变磷酸酶的过表达导致细胞增殖和血清诱导的有丝分裂增强，表明突变导致显性负性蛋白的产生。突变LMW-PTP表达细胞的分析使我们能够证明LMW-PTP和血小板衍生生长因子受体之间的关联似乎是高度特异性的，我们的数据表明，LMW-PTP对磷酸化血小板衍生生长因子受体的催化作用。
Low M(r) phosphotyrosine protein phosphatase (LMW-PTP) is a 18 kDa cytosolic enzyme widely distributed in eukaryotic cells, LMW-PTP catalyses the hydrolysis of phosphotyrosine residues and overexpression of the enzyme in normal and transformed cells inhibits cell proliferation, Site directed mutagenesis, together with crystallographic studies, have contributed to clarify the catalytic mechanism, which involves the active site signature sequence C(12)XXXXXR(18), a main feature of all PTPase family members, In order to identify the LMW-PTP substrate/s we have expressed in NIH-3T3 cells a catalytically inert Cys(12) to Ser phosphatase mutant which has preserved its capacity for substrate binding, Overexpression of the mutant phosphatase leads to enhanced cell proliferation and serum induced mitogenesis, indicating that the mutation results in the production of a dominant negative protein, Analysis of mutant LMW-PTP expressing cells has enabled us to demonstrate an association between LMW-PTP and platelet derived growth factor receptor that appears to be highly specific, Our data suggest a catalytic action of LMW-PTP on the phosphorylated platelet derived growth factor receptor.