Vasopressin up-regulates the expression of growth-related immediate-early genes via two distinct EGF receptor transactivation pathways.
Activation of V(1a) receptor triggers the expression of growth-related immediate-early genes (IEGs), including c-Fos and Egr-1. We found that pre-treatment of rat vascular smooth muscle A-10 cell line with the EGF receptor inhibitor AG1478 or the over-expression of an EGFR dominant negative mutant (HEBCD533) blocked the vasopressin-induced expression of IEGs, suggesting that activation of these early genes mediated by V(1a) receptor is via transactivation of the EGF receptor. Importantly, the inhibition of the metalloproteinases, which catalyzed the shedding of the EGF receptor agonist HB-EGF, selectively blocked the vasopressin-induced expression c-Fos. On the other hand, the inhibition of c-Src selectively blocked the vasopressin-induced expression of Egr-1. Interestingly, in contrast to the expression of c-Fos, the expression of Egr-1 was mediated via the Ras/MEK/MAPK-dependent signalling pathway. Vasopressin-triggered expression of both genes required the release of intracellular calcium, activation of PKC and beta-arrestin 2. These findings demonstrated that vasopressin up-regulated the expression of c-Fos and Erg-1 via transactivation of two distinct EGF receptor-dependent signalling pathways.
Department of Physiology, Universidad Austral de Chile, Valdivia, Chile.
Lida Q
LQ
Fuentes
Carlos E
CE
Reyes
José M
JM
Sarmiento
Carolina I
CI
Villanueva
Carlos D
CD
Figueroa
Javier
J
Navarro
Carlos B
CB
González
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D019390:Arrestins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D019938:Cyclin D1 / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics*; D017781:Genes, Immediate-Early; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017483:Receptors, Vasopressin / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605257:Arrb2 protein, rat; D019390:Arrestins; D051766:Early Growth Response Protein 1; D016760:Proto-Oncogene Proteins c-fos; D017483:Receptors, Vasopressin; D016160:Retinoblastoma Protein; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D001127:Arginine Vasopressin; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D002118:Calcium