The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling
The tyrosine phosphatase SHP-1 associates with the sst2 somatostatin receptor and is an essential component of sst2-mediated inhibitory growth signaling
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DOI：
10.1074/jbc.272.39.24448
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发表时间：
1997-09-26
影响因子：
4.8
通讯作者：
Susini, C
中科院分区：
文献类型：
--
作者：
Lopez, F;Esteve, JP;Susini, C
生长抑素受体Sst2是G(I)蛋白偶联受体家族中的一员，它的激活导致参与SstZ介导的生长抑制信号的蛋白酪氨酸磷酸酶活性的刺激。在这里，我们报道了SHP-1，一种胞质蛋白酪氨酸磷酸酶，含有两个与Sst2构成相关的Src同源2结构域，作为SHP-1与Sst2蛋白共沉淀的证据。生长抑素激活Sst2导致SHP-1从Sst2迅速解离，同时SHP-1活性增加，SHP-1在对照细胞的酪氨酸上被磷酸化，生长抑素诱导SHE酶的酪氨酸残基快速瞬时去磷酸化。生长抑素对SIIP-I活性的刺激可被百日咳毒素预处理所阻断，G(Iα3)被抗Sst2和抗SHP-1抗体特异性免疫沉淀，生长抑素诱导G(Iα3)从Sst2迅速解离，提示G(Iα3)可能参与Sst2-SHP-1复合体的形成，最终抑制共表达Sst2和SHP-1的细胞的增殖，这种作用在共表达Sst2和催化失活的SHP-1(C453S突变体)细胞中被抑制。我们的数据证明SHP-1是与Sst2相关的酪氨酸磷酸酶，并表明该酶可能是Sst2介导的抗分裂信号的初始关键转导因子。
Activation of the somatostatin receptor sst2, a member of the G(i) protein-coupled receptor family, results in the stimulation of a protein-tyrosine phosphatase activity involved in the sstZ-mediated growth inhibitory signal, Here, we report that SHP-1, a cytoplasmic protein-tyrosine phosphatase containing two Src homology 2 domains constitutively associated with sst2 as evidence by coprecipitation of SHP-1 pro-rein with sst2, in Chinese hamster ovary cells coexpressing sst2 and SHP-1. Activation of sst2 by somatostatin resulted in a rapid dissociation of SHP-1 from sst2 accompanied by an increase of SHP-1 activity, SHP-1 was phosphorylated on tyrosine in control cells and somatostatin induced a rapid and transient dephosphorylation on tyrosine residues of She enzyme. Stimulation of SIIP-I activity by somatostatin was abolished by pertussis toxin pretreatment of cells, G(i alpha 3) was specifically immunoprecipitated by anti-sst2 and anti-SHP-1 antibodies, and somatostatin induced a rapid dissociation of G(i alpha 3) from sst2, suggesting that G(i alpha 3) may be involved in the sst2-SHP-1 complexes, Finally, somatostatin inhibited the proliferation of cells coexpressing sst2 and SHP-1, and this effect was suppressed in cells coexpressing sst2 and the catalytic inactive SHP-1 (C453S mutant). Our data identify SHP-1 as the tyrosine phosphatase associated with sst2 and demonstrate that this enzyme may be an initial key transducer of the antimitogenic signaling mediated by sst2.