生长激素信号通路。

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Carter-Su C,施瓦茨J, Argetsinger LS

生长激素信号通路。

增长霍恩IGF研究》2016年6月,28:11-5。doi: 10.1016 / j.ghir.2015.09.002。Epub 2015 9月10。

PubMed ID

26421979 (在PubMed

]

文摘

20多年前,我们的实验表明,生长激素(GH)通过GH receptor-associated酪氨酸激酶JAK2信号。我们表明,GH绑定的膜结合受体增强约束力JAK2 GHR,激活JAK2和刺激酪氨酰JAK2和GHR的磷酸化。激活JAK2 / GHR复杂招募各种信号的蛋白质,从而启动多个信号通路和细胞反应。这些蛋白质和途径包括:1)统计转录因子涉及多种基因的表达,包括胰岛素样生长因子1基因编码;2)自燃导致适配器蛋白质激活grb2-SOS-Ras-Raf-MEK-ERK1, 2通道;3)胰岛素受体底物蛋白质涉及phosphatidylinositol-3-kinase和Akt通路;4)信号调节蛋白α,一种跨膜支架蛋白,成员包括蛋白质酪氨酸磷酸酶SHP2;5)SH2B1,脚手架蛋白能激活JAK2和提高GH肌动蛋白细胞骨架的监管。我们最近的工作都集中在SH2B1的功能。我们已经表明,SH2B1beta招募和GH JAK2磷酸化的反应。 SH2B1 localizes to the plasma membrane, cytoplasm and focal adhesions; it also cycles through the nucleus. SH2B1 regulates the actin cytoskeleton and promotes GH-dependent motility of RAW264.7 macrophages. Mutations in SH2B1 have been found in humans exhibiting severe early-onset childhood obesity and insulin resistance. These mutations impair SH2B1 enhancement of GH-induced macrophage motility. As SH2B1 is expressed ubiquitously and is also recruited to a variety of receptor tyrosine kinases, our results raise the possibility that effects of SH2B1 on the actin cytoskeleton in various cell types, including neurons, may play a role in regulating body weight.

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