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Transforming growth factor β 2 stimulates acute and chronic activation of the mitogen‐activated protein kinase cascade in rat renal mesangial cells
Author(s) -
Huwiler Andrea,
Pfeilschifter Josef
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)01132-x
Subject(s) - mitogen activated protein kinase , mitogen activated protein kinase kinase , map kinase kinase kinase , mesangial cell , kinase , ask1 , protein kinase a , cyclin dependent kinase 9 , microbiology and biotechnology , mitogen activated protein kinase 3 , activator (genetics) , mapk7 , c raf , map2k7 , biology , cyclin dependent kinase 2 , chemistry , endocrinology , biochemistry , kidney , receptor
Exposure of rat glomerular mesangial cells to transforming growth factor β 2 (TGFβ 2 ) stimulates a biphasic mitogen‐activated protein kinase (MAP kinase) activation. A rapid increase in activity (maximal at 10 min) is followed by a second persistent level of activity which steadily increases over 24 h. The second peak of MAP kinase activity is markedly attenuated by the protein synthesis inhibitor cycloheximide and consequently is paralleled by a pronounced de‐novo synthesis of p42 and p44 MAP kinases as measured by immunoprecipitation of [ 35 S]methionine‐labeled mesangial cells. In addition, an increased de‐novo synthesis of MAP kinase kinase (MEK), the upstream activator of MAP kinase, is observed in response to TGFβ 2 stimulation. We propose that TGFβ‐induced activation and de‐novo synthesis of MAP kinases and MEK is important for the multifunctional actions of this cytokine in mesangial cells and its role in disease states characterized by excessive fibrosis.