Dance Marie, Montagner Alexandra, Salles Jean-Pierre, Yart Armelle, Raynal Patrick
INSERM U563, Département Lipoprotéines et Médiateurs Lipidiques, Site Purpan, Toulouse, France.
Cell Signal. 2008 Mar;20(3):453-9. doi: 10.1016/j.cellsig.2007.10.002. Epub 2007 Oct 11.
Shp2 is a ubiquitous tyrosine phosphatase containing Src Homology 2 domains which plays major biological functions in response to various growth factors, hormones or cytokines. This is essentially due to its particularity of promoting the activation of the Ras/Mitogen-activated protein kinase pathway. Recent progresses have been made in the understanding of the molecular mechanisms involved in this regulation. We review here, and discuss the physiological relevance, of the following molecular functions of Shp2 that have been proposed to couple the phosphatase to Ras activation: promoter of Grb2/Sos recruitment through direct binding to Grb2, binding partner and regulator of SHPS-1, negative regulator of Sprouty, negative regulator of RasGAP recruitment, and activator of Src through dephosphorylation of Src-regulatory proteins.
Shp2是一种普遍存在的含Src同源2结构域的酪氨酸磷酸酶，在对各种生长因子、激素或细胞因子的应答中发挥主要生物学功能。这主要归因于其促进Ras/丝裂原活化蛋白激酶途径激活的特性。在理解参与这种调节的分子机制方面已取得了最新进展。在此，我们回顾并讨论已提出的Shp2的以下分子功能的生理相关性，这些功能将磷酸酶与Ras激活联系起来：通过直接结合Grb2促进Grb2/Sos募集、SHPS-1的结合伴侣和调节剂、Sprouty的负调节剂、RasGAP募集的负调节剂以及通过使Src调节蛋白去磷酸化来激活Src。
