| First Author | Brandmayr J | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 27 | Pages | 22584-92 |
| PubMed ID | 22589548 | Mgi Jnum | J:323278 |
| Mgi Id | MGI:6843095 | Doi | 10.1074/jbc.M112.366484 |
| Citation | Brandmayr J, et al. (2012) Deletion of the C-terminal phosphorylation sites in the cardiac beta-subunit does not affect the basic beta-adrenergic response of the heart and the Ca(v)1.2 channel. J Biol Chem 287(27):22584-92 |
| abstractText | Phosphorylation of the cardiac beta subunit (Ca(v)beta(2)) of the Ca(v)1.2 L-type Ca(2+) channel complex has been proposed as a mechanism for regulation of L-type Ca(2+) channels by various protein kinases including PKA, CaMKII, Akt/PKB, and PKG. To test this hypothesis directly in vivo, we generated a knock-in mouse line with targeted mutation of the Ca(v)beta(2) gene by insertion of a stop codon after proline 501 in exon 14 (mouse sequence Cacnb2; betaStop mouse). This mutation prevented translation of the Ca(v)beta(2) C terminus that contains the relevant phosphorylation sites for the above protein kinases. Homozygous cardiac betaStop mice were born at Mendelian ratio, had a normal life expectancy, and normal basal L-type I(Ca). The regulation of the L-type current by stimulation of the beta-adrenergic receptor was unaffected in vivo and in cardiomyocytes (CMs). betaStop mice were cross-bred with mice expressing the Ca(v)1.2 gene containing the mutation S1928A (SAbetaStop) or S1512A and S1570A (SFbetaStop) in the C terminus of the alpha(1C) subunit. The beta-adrenergic regulation of the cardiac I(Ca) was unaltered in these mouse lines. In contrast, truncation of the Ca(v)1.2 at Asp(1904) abolished beta-adrenergic up-regulation of I(Ca) in murine embryonic CMs. We conclude that phosphorylation of the C-terminal sites in Ca(v)beta(2), Ser(1928), Ser(1512), and Ser(1570) of the Ca(v)1.2 protein is functionally not involved in the adrenergic regulation of the murine cardiac Ca(v)1.2 channel. |
