Evidence for the involvement of protein kinase activity in transforming growth factor-beta signal transduction
Autor: | Masahiko Ohtsuki, Joan Massagué |
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Rok vydání: | 1992 |
Předmět: |
medicine.drug_class
Blotting Western Mitogen-activated protein kinase kinase Retinoblastoma Protein Cell Line MAP2K7 Transforming Growth Factor beta medicine Animals c-Raf Phosphorylation Protein kinase A Protein Kinase Inhibitors Molecular Biology Protein kinase C Serine/threonine-specific protein kinase biology Cyclin-dependent kinase 2 Cell Biology Protein kinase inhibitor Molecular biology Plasminogen Inactivators Gene Expression Regulation biology.protein Tetradecanoylphorbol Acetate Protein Kinases Cell Division Signal Transduction Research Article |
Zdroj: | Molecular and Cellular Biology. 12:261-265 |
ISSN: | 1098-5549 0270-7306 |
Popis: | Transforming growth factor-beta 1 (TGF-beta 1) rapidly increases the expression of junB transcription factor and plasminogen activator inhibitor-1 (PAI-1) and prevents the cell cycle-dependent phosphorylation of the RB retinoblastoma susceptibility gene product during late G1 phase in Mv1Lu lung epithelial cells. These responses are shown in this report to be blocked by the potent serine/threonine protein kinase inhibitor, H7, added with TGF-beta 1. Added alone, H7 does not alter the basal junB or PAI-1 mRNA levels, the deposition of PAI-1 into the extracellular matrix, or the phosphorylation of RB in late G1 phase, suggesting that this inhibitor does not have a general nonspecific effect on the cell. The analogs H8 and H9, which are preferential inhibitors of cyclic nucleotide-dependent protein kinases, are fivefold less potent than H7 as inhibitors of the TGF-beta response. The PAI-1 response to TGF-beta 1 is not affected by the simultaneous addition of staurosporine, which is a protein kinase C inhibitor, or by the prolonged preincubation of cells with phorbol 12-myristate 13-acetate, which down-regulates protein kinase C. The results suggest the possibility that H7 and its analogs block various early TGF-beta responses by inhibiting a protein serine/threonine kinase(s). |
Databáze: | OpenAIRE |
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