Targeted disruption of the tyrosine phosphatase PTPα leads to constitutive downregulation of the kinases Src and Fyn

被引:176
|
作者
Ponniah, S
Wang, DZM
Lim, KL
Pallen, CJ
机构
[1] Inst Mol & Cell Biol, Cell Regulat Lab, Singapore 117609, Singapore
[2] Inst Mol & Cell Biol, In Vivo Model Syst Unit, Singapore 117609, Singapore
关键词
D O I
10.1016/S0960-9822(99)80238-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A role for the receptor-like protein tyrosine phosphatase alpha (PTP alpha) in regulating the kinase activity of Src family members has been proposed because ectopic expression of PTPa enhances the dephosphorylation and activation of Src and Fyn [1-3]. We have generated mice lacking catalytically active PTP alpha to address the question of whether PTPa is a physiological activator of Src and Fyn, and to investigate its other potential functions in the context of the whole animal. Mice homozygous for the targeted PTP alpha allele (PTP alpha(-/-)) and lacking detectable PTP alpha protein exhibited no gross phenotypic defects. The kinase activities of Src and Fyn were significantly reduced in PTP alpha(-/-) mouse brain and primary embryonic fibroblasts, and this correlated with enhanced phosphorylation of the carboxy-terminal regulatory Tyr527 of Src in PTP alpha(-/-) mice. Thus, PTP alpha is a physiological positive regulator of the tyrosine kinases Src and Fyn, Increased tyrosine phosphorylation of several unidentified proteins was also apparent in PTP alpha(-/-) mouse brain lysates. These may be PTP alpha substrates or downstream signaling proteins. Taken together, the results indicate that PTP alpha has a dual function as a positive and negative regulator of tyrosine phosphorylation events, increasing phosphotyrosyl proteins through activation of Src and Fyn, and directly or indirectly removing tyrosine phosphate from other unidentified proteins, (C) Elsevier Science Ltd ISSN 0960-9822.
引用
收藏
页码:535 / 538
页数:4
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