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首页> 外文期刊>Molecular and Cellular Biology >The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function.
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The common src homology region 2 domain of cytoplasmic signaling proteins is a positive effector of v-fps tyrosine kinase function.

机译：细胞质信号蛋白的常见src同源区域2结构域是v-fps酪氨酸激酶功能的正效应子。

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摘要

A conserved noncatalytic domain SH2 (for src homology region 2) is located immediately N terminal to the kinase domains of all cytoplasmic protein-tyrosine kinases. We found that the wild-type v-fps SH2 domain stimulated the enzymatic activity of the adjacent kinase domain 10-fold and functioned as a powerful positive effector of catalytic and transforming activities within the v-fps oncoprotein (P130gag-fps). Partial proteolysis of P130gag-fps and supporting genetic data indicated that the v-fps SH2 domain exerts its effect on catalytic activity through an intramolecular interaction with the kinase domain. Amino acid alterations in the SH2 domain that impaired kinase function interfered with association of the SH2 domain with the kinase domain. Deletion of a conserved octapeptide motif converted the v-fps SH2 domain from an activator to an inhibitor of tyrosine kinase activity. This latent inhibitory activity of v-fps SH2 has functional implications for phospholipase C-gamma and p21ras GTPase-activating protein, both of which have two distinct SH2 domains suggestive of complex regulation. In addition to regulating the specific activity of the kinase domain, the SH2 domain of P130gag-fps was also found to be required for the tyrosine phosphorylation of specific cellular proteins, notably polypeptides of 124 and 62 kilodaltons. The SH2 domain therefore appears to play a dual role in regulation of kinase activity and recognition of cellular substrates.
机译：保守的非催化结构域SH2（对于src同源性区域2）位于所有细胞质蛋白-酪氨酸激酶的激酶结构域的N末端。我们发现野生型v-fps SH2结构域可将相邻激酶结构域的酶促活性提高10倍，并在v-fps癌蛋白（P130gag-fps）内起催化和转化活性的强大正效应器作用。 P130gag-fps的部分蛋白水解和支持的遗传数据表明，v-fps SH2结构域通过与激酶结构域的分子内相互作用对催化活性发挥作用。 SH2结构域中影响激酶功能的氨基酸改变会干扰SH2结构域与激酶结构域的缔合。保守的八肽基序的缺失将v-fps SH2结构域从活化剂转变为酪氨酸激酶活性的抑制剂。 v-fps SH2的这种潜在抑制活性对磷脂酶C-γ和p21ras GTPase激活蛋白具有功能性暗示，二者均具有两个不同的SH2域，提示复杂的调节。除了调节激酶结构域的比活性之外，还发现P130gag-fps的SH2结构域是特定细胞蛋白（尤其是124和62道尔顿的多肽）的酪氨酸磷酸化所必需的。因此，SH2结构域似乎在调节激酶活性和识别细胞底物方面起着双重作用。

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