| First Author | Rakhilin SV | Year | 2004 |
| Journal | Science | Volume | 306 |
| Issue | 5696 | Pages | 698-701 |
| PubMed ID | 15499021 | Mgi Jnum | J:94124 |
| Mgi Id | MGI:3511253 | Doi | 10.1126/science.1099961 |
| Citation | Rakhilin SV, et al. (2004) A network of control mediated by regulator of calcium/calmodulin-dependent signaling. Science 306(5696):698-701 |
| abstractText | Calmodulin (CaM) is a major effector for the intracellular actions of Ca2+ in nearly all cell types. We identified a CaM-binding protein, designated regulator of calmodulin signaling (RCS). G protein-coupled receptor (GPCR)-dependent activation of protein kinase A (PKA) led to phosphorylation of RCS at Ser55 and increased its binding to CaM. Phospho-RCS acted as a competitive inhibitor of CaM-dependent enzymes, including protein phosphatase 2B (PP2B, also called calcineurin). Increasing RCS phosphorylation blocked GPCR- and PP2B-mediated suppression of L-type Ca2+ currents in striatal neurons. Conversely, genetic deletion of RCS significantly increased this modulation. Through a molecular mechanism that amplifies GPCR- and PKA-mediated signaling and attenuates GPCR- and PP2B-mediated signaling, RCS synergistically increases the phosphorylation of key proteins whose phosphorylation is regulated by PKA and PP2B. |
