Grb10,积极刺激血小板源生长因子BB -信号适配器,胰岛素样生长因子I -, insulin-mediated有丝分裂发生。
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王J,戴H Yousaf N, Moussaif M,邓Y, Boufelliga,偶像,里昂我,里德尔H
Grb10,积极刺激血小板源生长因子BB -信号适配器,胰岛素样生长因子I -, insulin-mediated有丝分裂发生。
摩尔细胞杂志。1999年9月,19 (9):6217 - 28。
- PubMed ID
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10454568 (在PubMed]
- 文摘
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Grb10被描述为一个细胞伙伴几受体酪氨酸激酶,包括胰岛素受体(IR)和胰岛素样生长因子I (IGF-I)受体(IGF-IR)。其细胞的作用仍不清楚和积极的细胞有丝分裂发生的抑制作用取决于上下文被牵连。我们已经测试了其他促有丝分裂的受体酪氨酸激酶作为公认的Grb10伙伴和已经确定了激活的血小板源生长因子(PDGF)受体β(PDGFRbeta),肝细胞生长因子受体(遇到),和纤维母细胞生长因子受体作为候选人。我们有映射Y771 PDFGRbeta网站,参与协会通过其与Grb10 SH2域。我们有进一步研究的假定的角色Grb10有丝分裂发生在四个独立的实验策略和发现所有一贯建议作为一个积极的,刺激信号适配器正常成纤维细胞。(我)完成Grb10表达式从cDNA ecdysone-regulated瞬时表达系统的刺激PDGF-BB -, IGF-I,胰岛素——但不是全身的表皮生长因子(EGF) DNA合成在一个时尚细胞和细胞龛之间蜕皮激素剂量反应关系。(2)显微镜下注射(显性负)Grb10 SH2域的干扰PDGF-BB insulin-induced DNA合成。(3)替代实验基于cell-permeable融合肽与果蝇antennapedia homeodomain有效地遍历培养细胞的质膜。一个cell-permeable Grb10 SH2域同样干扰PDGF-BB, IGF-I和insulin-induced DNA合成。相比之下,cell-permeable Grb10 Pro-rich假定SH3域绑定地区干扰IGF-I——和胰岛素——但不是PDGF-BB——或者EGF-induced DNA合成。 (iv) Transient overexpression of complete Grb10 increased whereas cell-permeable Grb10 SH2 domain fusion peptides substantially decreased the cell proliferation rate (as measured by cell numbers) in normal fibroblasts. These experimental strategies independently suggest that Grb10 functions as a positive, stimulatory, mitogenic signaling adapter in PDGF-BB, IGF-I, and insulin action. This function appears to involve the Grb10 SH2 domain, a novel sequence termed BPS, and the Pro-rich putative SH3 domain binding region in IGF-I- and insulin-mediated mitogenesis. In contrast, PDGF-BB-mediated mitogenesis appears to depend on the SH2 but not on the Pro-rich region and may involve other, unidentified Grb10 domains. Distinct protein domains may help to define specific Grb10 functions in different signaling pathways.