Pallen Catherine J
Department of Pediatrics, BC Research Institute for Children's & Women's Health, University of British Columbia, 3102-950 West 28 Ave, Vancouver, British Columbia, V5Z 4H4, Canada.
Curr Top Med Chem. 2003;3(7):821-35. doi: 10.2174/1568026033452320.
This review discusses progress made over the past 10+ years in elucidating the properties, regulation, and function of protein tyrosine phosphatase alpha (PTPalpha). It is apparent from studies in knockout mice and diverse cell lines that the major action of PTPalpha is as a positive regulator of src and src family kinases. PTPalpha dephosphorylates and activates src. In this manner it affects transformation and tumourigenesis, inhibition of proliferation and cell cycle arrest, mitotic activation of src, integrin signaling, neuronal differentiation and outgrowth, and ion channel activity. PTPalpha may well modulate additional processes, including insulin signaling, and have other targets besides src family kinases. As an important modulator of several specific cell signaling pathways, PTPalpha has promise as a target for drug discovery. Continued research on the physiological and pathological activities of PTPalpha is necessary to define the therapeutic potential of PTPalpha-directed pharmacologicals.
本综述讨论了过去十余年在阐明蛋白酪氨酸磷酸酶α(PTPα)的特性、调节及功能方面所取得的进展。从基因敲除小鼠及多种细胞系的研究中可以明显看出,PTPα的主要作用是作为src和src家族激酶的正向调节因子。PTPα使src去磷酸化并激活src。通过这种方式,它影响细胞转化和肿瘤发生、抑制增殖和细胞周期停滞、src的有丝分裂激活、整合素信号传导、神经元分化和生长以及离子通道活性。PTPα很可能还调节包括胰岛素信号传导在内的其他过程,并且除src家族激酶外还有其他靶点。作为几种特定细胞信号通路的重要调节因子,PTPα有望成为药物研发的靶点。持续研究PTPα的生理和病理活性对于确定针对PTPα的药物的治疗潜力是必要的。