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Tyrosine nitration of L‐type Ca channels prevents activation of the cyclic AMP Response Element (CRE)
Author(s) -
Kang Minho,
Akbarali Hamid I
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1000.20
Subject(s) - creb , tyrosine phosphorylation , forskolin , phosphorylation , chemistry , microbiology and biotechnology , tyrosine , signal transduction , tyrosine kinase , ionomycin , biochemistry , biology , transcription factor , gene , receptor , in vitro
Calcium influx through Cav1.2 has been implicated in signal transduction and gene expression. We have recently shown that colonic inflammation results in decreased Ca currents due to nitration of c‐terminal tyrosine residues that prevents src‐kinase mediated phosphorylation. In hCav1.2b transfected cells, depolarization by KCl and/or treatement with the Ca channel agonist BayK8644 induced phosphorylation of the cAMP response binding protein (CREB). Phospho‐CREB binds to CRE sites on promoter regions of several genes. A dual luciferase assay was used to determine activation of CRE in hCav1.2b transfected cells. CRE activation was increased by 2.4‐fold by KCl‐induced depolarization that was blocked by nifedipine. Nitration of hCav1.2b by peroxynitrite (150 uM) prevented KCl induced CRE activation. Both Forskolin and Ionomycin enhanced CRE activation by 2.8‐fold. Mutation of c‐terminal tyrosine residues (Y1837‐1861‐2134F) prevented CRE activation. These data suggest that tyrosine phosphorylation of the COOH terminus of Cav1.2 plays an important role in the downstream signaling for the activation of transcription factors. Supported by NIDDK046367.