Involvement of the platelet‐derived growth factor receptor in angiotensin II‐induced activation of extracellular regulated kinases 1 and 2 in human mesangial cells

FEBS Letters

Piiper, Albrecht¹  Mondorf, Ulrich F.²  Geiger, Helmut²  Herrero, Martina²  Zeuzem, Stefan¹ 

[1] Department of Medicine, Division of Gastroenterology, Johann Wolfgang Goethe-University, Frankfurt am Main, Germany;Department of Medicine, Division of Nephrology, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

关键词: Angiotensin II;    Platelet-derived growth factor receptor;    Tyrosine kinase;    Extracellular regulated protein kinase;    Grb2;    Shc;   

DOI  :  10.1016/S0014-5793(00)01433-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In mesangial cells angiotensin II (Ang II) has been shown to activate extracellular regulated kinases 1 and 2 (ERK1/2). Here, we studied the role of the epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor (PDGFR) in Ang II-induced ERK1/2 activation in human mesangial cells. Ang II induced activation of ERK1/2 via the AT₁ receptor, and this response was blocked by the PDGFR-selective tyrosine kinase inhibitor AG1295, but not by AG1478, an EGFR-selective tyrosine kinase inhibitor, indicating participation of the PDGFR, but not of the EGFR in Ang II-induced ERK1/2 activation. In agreement with this assumption, Ang II caused tyrosine phosphorylation of the PDGFR and the adapter protein Shc in an AG1295-sensitive fashion. In conclusion, our data show that Ang II-induced activation of mitogenic signalling cascade in human mesangial cells involves ligand-independent activation of the PDGFR, but not of the coexpressed EGFR.

【 授权许可】

Unknown