COMPARTMENTALIZATION OF SHC, GRB2 AND MSOS, AND HYPERPHOSPHORYLATION OF RAF-1 BY EGF BUT NOT INSULIN IN LIVER PARENCHYMA
COMPARTMENTALIZATION OF SHC, GRB2 AND MSOS, AND HYPERPHOSPHORYLATION OF RAF-1 BY EGF BUT NOT INSULIN IN LIVER PARENCHYMA
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DOI：
10.1002/j.1460-2075.1994.tb06747.x
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发表时间：
1994-09-15
期刊：
影响因子：
11.4
通讯作者：
BERGERON, JJM
中科院分区：
文献类型：
--
作者：
DIGUGLIELMO, GM;BAASS, PC;BERGERON, JJM
大鼠肝实质含有等量的表皮生长因子(EGF)和胰岛素受体。在给予饱和剂量的EGF(10微克/100克体重)后，受体的内化(T1/2类似于1.1分钟)与其在残基1173位的酪氨酸磷酸化一致，受体募集的适配蛋白SHC，它的酪氨酸磷酸化及其与Grb2和RAS鸟嘌呤核苷酸交换因子MSO的关系，主要在内体中。这导致了一个由酪氨酸磷酸化的SHC、Grb2和MSO组成的复合体的细胞质池。在单次注射EGF后，Raf-1迁移率显著降低，持续60min，证明这些成分与RAS激活有关。虽然给予胰岛素(15微克/100克体重)导致胰岛素受体β亚单位酪氨酸的磷酸化和内化，但几乎没有检测到SHC的酪氨酸磷酸化、Grb2的募集、与MSO的复合体的结合或Raf-1的任何可检测到的变化。因此，在体内正常的生理靶细胞中，不同的信号通路是在EGF或胰岛素受体激活后实现的，这种特异性的调节很可能发生在内体的位置。
Rat liver parenchyma harbors equal numbers of epidermal growth factor (EGF) and insulin receptors. Following administration of a saturating dose of EGF (10 mu g/100 g body weight), there was a rapid (t1/2 similar to 1.1 min) internalization of receptor coincident with its tyrosine phosphorylation at residue 1173 and receptor recruitment of the adaptor protein SHC, its tyrosine phosphorylation and its association with GRB2 and the Ras guanine nucleotide exchange factor, mSOS, largely in endosomes. This led to a cytosolic pool of a complex of tyrosine-phosphorylated SHC, GRB2 and mSOS. It was demonstrated that these constituents were linked to Ras activation by the characteristic decrease in Raf-1 mobility on SDS-PAGE, which was maintained for 60 min after a single bolus of administered EGF. While insulin administration (15 mu g/100 g body weight) led to insulin receptor beta-subunit tyrosine phosphorylation and internalization, there was little detectable tyrosine phosphorylation of SHC, recruitment of GRB2, association of a complex with mSOS or any detectable change in the mobility of Raf-1. Therefore, in normal physiological target cells in vivo, distinct signaling pathways are realized after EGF or insulin receptor activation, with regulation of this specificity most probably occurring at the locus of the endosome.