Protein tyrosine phosphatase activity modulation by endothelin‐1 in rabbit platelets

FEBS Letters

Calcerrada, M.Carmen²  Liras, Antonio¹  Gargiulo, Laura²  Catalán, R.Edgardo¹  Martı́nez, Ana M² 

[1] Departamento de Biologı́a Molecular, Centro de Biologı́a Molecular ‘Severo Ochoa’ (CSIC‐UAM), Universidad Autónoma de Madrid, E–28049 Madrid, Spain;Departamento de Bioquı́mica y Biologı́a Molecular I, Facultad de Quı́micas, Universidad Complutense de Madrid, E–28040 Madrid, Spain

关键词: Endothelin-1;    Protein tyrosine phosphatase;    Focal adhesion kinase protein;    Rabbit platelet;   

DOI  :  10.1016/S0014-5793(96)01405-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Protein tyrosine phosphorylation, modulated by the rate of both protein tyrosine kinase and protein tyrosine phosphatase activities, is critical for cellular signal transduction cascades. We report that endothelin-1 stimulation of rabbit platelets resulted in a dose- and time-dependent tyrosine phosphorylation of four groups of proteins in the molecular mass ranges of 50, 60, 70–100 and 100–200 kDa and that one of these corresponds to focal adhesion kinase. This effect is also related to the approximately 60% decrease in protein tyrosine phosphatase activity. Moreover, this inhibited activity was less sensitive to orthovanadate. In the presence of forskolin that increases the cAMP level a dose-dependent inhibition of the endothelin-stimulated tyrosine phosphorylation of different protein substrates and a correlation with an increase in the protein tyrosine phosphatase activity (11.6-fold compared to control) have been found. Further studies by immunoblotting of immunoprecipitated soluble fraction with anti-protein tyrosine phosphatase-1C from endothelin-stimulated platelets have demonstrated that the tyrosine phosphorylation of platelet protein tyrosine phosphatase-1C is correlated with the decrease in its phosphatase activity. As a consequence, modulation and regulation by endothelin-1 in rabbit platelets can be proposed through a cAMP-dependent pathway and a tyrosine phosphorylation process that may affect some relevant proteins such as focal adhesion kinase.

【 授权许可】

Unknown