Vascular types I and II transforming growth factor-beta receptor expression: differential dependency on tyrosine kinases during induction by TGF-beta.
Recent evidence indicates that the type II transforming growth factor-beta (TGF-beta) receptor (TbetaRII) is a serine-threonine-tyrosine kinase. However, the significance of its tyrosine kinase is unclear. We investigated in vascular smooth muscle cells the effects of tyrosine kinase inhibition on the expression of TGF-beta receptor types I (ALK-5) and II (TbetaRII) mRNA, induced by TGF-beta1. TGF-beta1 elevated ALK-5 mRNA levels 5-fold; essentially similar TGF-beta1-dependent elevations were observed with growth factors, PDGF-BB and FGF-2. The tyrosine kinase inhibitor genistein abolished these TGF-beta1 and growth factor responses. TGF-beta1 also elevated TbetaRII mRNA levels which were not inhibited by genistein. We conclude that tyrosine kinases participate in defining how cells respond to TGF-beta.
Ward
M R
MR
Cell Biology Laboratory, Baker Medical Research Institute and Alfred Hospital, Prahran, Vic., Australia. mward@baker.edu.au
Agrotis
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Jennings
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Bobik
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D030201:Activin Receptors, Type I; D000818:Animals; D000077214:Becaplermin; D017536:Carotid Artery, Common / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D017540:Tunica Media / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat