SH2 AND SH3 DOMAINS - ELEMENTS THAT CONTROL INTERACTIONS OF CYTOPLASMIC SIGNALING PROTEINS
SH2 AND SH3 DOMAINS - ELEMENTS THAT CONTROL INTERACTIONS OF CYTOPLASMIC SIGNALING PROTEINS
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DOI：
10.1126/science.1708916
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发表时间：
1991-05-03
期刊：
影响因子：
56.9
通讯作者：
PAWSON, T
中科院分区：
文献类型：
--
作者：
KOCH, CA;ANDERSON, D;PAWSON, T
Src同源（SH）区2和3是在一系列由受体蛋白酪氨酸激酶调节的细胞质信号蛋白中保守的非催化结构域，所述受体蛋白酪氨酸激酶包括磷脂酶C-γ、Ras GT3（鸟苷三磷酸酶）激活蛋白和Src样酪氨酸激酶。这些信号传导蛋白的SH 2结构域结合酪氨酸磷酸化多肽，参与正常信号传导和细胞转化。酪氨酸磷酸化作为开关诱导SH 2结构域的结合，从而介导在质膜处或质膜附近形成异聚蛋白复合物。这些复合物的形成可能控制酪氨酸激酶对信号转导途径的激活。SH 3结构域是一个独特的基序，与SH 2一起，可以调节与细胞骨架和膜的相互作用。一些信号传导和转化蛋白含有未连接到任何已知催化元件的SH 2和SH 3结构域。这些非催化蛋白质可作为衔接子将酪氨酸激酶连接到特定的靶蛋白。这些观察结果表明，SH 2和SH 3域参与控制细胞内对生长因子刺激的反应。
Src homology (SH) regions 2 and 3 are noncatalytic domains that are conserved among a series of cytoplasmic signaling proteins regulated by receptor protein-tyrosine kinases, including phospholipase C-gamma, Ras GTPase (guanosine triphosphatase)-activating protein, and Src-like tyrosine kinases. The SH2 domains of these signaling proteins bind tyrosine phosphorylated polypeptides, implicated in normal signaling and cellular transformation. Tyrosine phosphorylation acts as a switch to induce the binding of SH2 domains, thereby mediating the formation of heteromeric protein complexes at or near the plasma membrane. The formation of these complexes is likely to control the activation of signal transduction pathways by tyrosine kinases. The SH3 domain is a distinct motif that, together with SH2, may modulate interactions with the cytoskeleton and membrane. Some signaling and transforming proteins contain SH2 and SH3 domains unattached to any known catalytic element. These noncatalytic proteins may serve as adaptors to link tyrosine kinases to specific target proteins. These observations suggest that SH2 and SH3 domains participate in the control of intracellular responses to growth factor stimulation.