Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development
Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development
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DOI：
10.1016/s0092-8674(00)81372-0
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发表时间：
1996-11-01
期刊：
影响因子：
64.5
通讯作者：
Ponzetto, C
中科院分区：
文献类型：
--
作者：
Maina, F;Casagranda, F;Ponzetto, C
肝细胞生长因子（HGF）及其受体Met酪氨酸激酶是胎盘、肝脏和肌肉发育的决定因素。在这里，我们表明，Met在体内的功能需要通过两个羧基末端酪氨酸信号。小鼠基因组中两个残基的突变导致胚胎死亡，胎盘，肝脏和四肢肌肉缺陷，模拟了met无效突变体的表型。相反，破坏Grb 2结合的共识允许发育进行到足月而不影响胎盘和肝脏，但引起肢体肌肉显著减少，并伴有次级纤维的普遍缺乏。这些数据表明，对Met信号传导的需求根据组织而变化，并揭示了HGF/Met在晚期肌生成中的新作用。
Hepatocyte growth factor (HGF) and its receptor, the Met tyrosine kinase, are determinants of placenta, liver, and muscle development. Here, we show that Met function in vivo requires signaling via two carboxyterminal tyrosines. Mutation of both residues in the mouse genome caused embryonal death, with placenta, liver, and limb muscle defects, mimicking the phenotype of met null mutants. In contrast, disrupting the consensus for Grb2 binding allowed development to proceed to term without affecting placenta and liver but caused a striking reduction in limb muscle coupled to a generalized deficit of secondary fibers. These data show that the requirements for Met signaling vary depending on the tissue and reveal a novel role for HGF/Met in late myogenesis.