Endothelin signalling and regulation of protein kinases in glomerular mesangial cells. Clin Sci (Lond) 2002 Aug;103 Suppl 48:132S-136S
Date
08/24/2002Pubmed ID
12193071DOI
10.1042/CS103S132SScopus ID
2-s2.0-0036671215 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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.
Author List
Sorokin A, Foschi M, Dunn MJAuthor
Andrey Sorokin PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenoviridaeAnimals
Cell Line, Transformed
Cells, Cultured
Endothelin-1
Enzyme Activation
Focal Adhesion Kinase 2
Genetic Vectors
Glomerular Mesangium
Humans
Mitogen-Activated Protein Kinases
Protein-Tyrosine Kinases
Rats
Signal Transduction
Transfection
Vasoconstrictor Agents
p38 Mitogen-Activated Protein Kinases
ras Proteins
