Zhang J, Somani A K, Siminovitch K A
Department of Medicine, University of Toronto, Ontario, Canada, M5G 1X5.
Semin Immunol. 2000 Aug;12(4):361-78. doi: 10.1006/smim.2000.0223.
The critical role for the SH2 domain-containing SHP-1 tyrosine phosphatase in regulating haemopoietic cell behaviour was initially revealed by data linking SHP-1 deficiency to the systemic autoimmunity and severe inflammation exhibited by motheaten mice. This discovery laid the groundwork for the identification of SHP-1 as an inhibitor of activation-promoting signalling cascades and for the coincident demonstration that protein tyrosine phosphatases (PTPs) such as SHP-1 show considerable specificity with respect to the mechanisms whereby they modulate the biochemical and biological sequelae of extracellular simulation. As outlined in this review, SHP-1 has now been implicated in the regulation of a myriad of signalling cascades and cell functions. As a result, the cumulative data generated from studies of this PTP have elucidated not only the functional relevance of SHP-1, but also a number of novel paradigms as to the molecular mechanisms whereby signalling cascades are regulated so as to either augment or abrogate specific cell behaviours.
含SH2结构域的SHP-1酪氨酸磷酸酶在调节造血细胞行为中的关键作用最初是通过将SHP-1缺陷与肌无力小鼠表现出的全身性自身免疫和严重炎症联系起来的数据揭示的。这一发现为将SHP-1鉴定为激活促进信号级联反应的抑制剂以及同时证明诸如SHP-1之类的蛋白酪氨酸磷酸酶（PTP）在调节细胞外刺激的生化和生物学后果的机制方面具有相当的特异性奠定了基础。如本综述所述，SHP-1现已涉及多种信号级联反应和细胞功能的调节。因此，从对这种PTP的研究中产生的累积数据不仅阐明了SHP-1的功能相关性，而且还阐明了关于信号级联反应如何被调节以增强或消除特定细胞行为的分子机制的一些新范例。
