alpha1B-Adrenergic receptor phosphorylation and desensitization induced by transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) induced alpha(1B)-adrenergic receptor phosphorylation in Rat-1 fibroblasts stably expressing these adrenoceptors. This effect of TGF-beta was rapid, reaching a maximum within 30 min and decreasing thereafter, and concentration-dependent (EC(50) 0.3 pM). The phosphoinositide 3-kinase inhibitors wortmannin and LY294002, and the protein kinase C inhibitors staurosporine, Ro 318220 and bisindolylmaleimide, blocked the effect of this growth factor. alpha(1B)-Adrenergic receptor phosphorylation was associated with desensitization, as indicated by a reduction in the adrenergic-mediated production of [(3)H]inositol phosphates. Phosphorylation of alpha(1B)-adrenergic receptors by TGF-beta was also observed in Cos-1 cells transfected with the receptor. Co-transfection of the dominant-negative mutant of the regulatory subunit of phosphoinositide 3-kinase (Deltap85) inhibited the phosphorylation of alpha(1B)-adrenergic receptors induced by TGF-beta. Our results indicate that activation of TGF-beta receptors induces alpha(1B)-adrenergic receptor phosphorylation and desensitization. The data suggest that phosphoinositide 3-kinase and protein kinase C play key roles in this effect of TGF-beta.
Romero-Avila
M Teresa
MT
Instituto de Fisiologi;a Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, México D.F. 04510.
Flores-Jasso
C Fabián
CF
García-Sáinz
J Adolfo
JA
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D002118:Calcium; D002867:Chromones; D004791:Enzyme Inhibitors; D007211:Indoles; D007295:Inositol Phosphates; D008301:Maleimides; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C; D018340:Receptors, Adrenergic, alpha-1; D018125:Receptors, Transforming Growth Factor beta; D019311:Staurosporine; D016212:Transforming Growth Factor beta; D000077191:Wortmannin; C547718:Adra1b protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C070515:bisindolylmaleimide I; C064758:Ro 31-8220