Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signalling.
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.
Zhang
J
J
Department of Medicine, University of Toronto, Ontario, Canada, M5G 1X5.
Somani
A K
AK
Siminovitch
K A
KA
D000818:Animals; D006801:Humans; D007109:Immunity; D047908:Intracellular Signaling Peptides and Proteins; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D015398:Signal Transduction / Q000276:immunology*; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases