The molecular mechanisms of endothelin (ET)-dependent activation of extracellular signal-regulated kinase (ERK)and p38 mitogen-activated protein (MAP) kinase were studied in rat and human renal glomerular mesangial cells. ET-1 induced a rapid and transient activation of Ras in renal mesangial cells, which was dependent upon the formation of the Shc/Grb2/Sos1 signalling complex and resulted in transient ERK activation. We have observed that Pyk2, a calcium-dependent cytoplasmic tyrosine kinase, was expressed in human renal mesangial cells and was tyrosine phosphorylated after ET-1 treatment. ET-1-induced activation of p38 MAPK pathway (but not ERK pathway) was inhibited in human and in rat glomerular mesangial cells expressing dominant-negative form of Pyk2, suggesting the engagement of Pyk2 in ET-1-mediated activation of p38 MAP kinase cascade. Contractive responsiveness of renal mesangial cells was shown to depend on activation of the p38 MAP kinases. Thus, p38 MAP kinase stimulation could perhaps partially account for ET-1 contractive properties, whereas ET-1-induced cell proliferation occurs primarily via Ras-dependent activation of the ERK.
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September 2002
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Conference Article|
September 01 2002
Endothelin signalling and regulation of protein kinases in glomerular mesangial cells
Andrey SOROKIN;
*Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, U.S.A.
Dr A. Sorokin (e-mail [email protected]).
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Marco FOSCHI;
Marco FOSCHI
†Department of Internal Medicine, University of Florence, v. le Morgagni 85, Florence 50141, Italy
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Michael J. DUNN
Michael J. DUNN
*Department of Medicine, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 132S–136S.
Citation
Andrey SOROKIN, Marco FOSCHI, Michael J. DUNN; Endothelin signalling and regulation of protein kinases in glomerular mesangial cells. Clin Sci (Lond) 1 September 2002; 103 (s2002): 132S–136S. doi: https://doi.org/10.1042/CS103S132S
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