| First Author | Fratini F | Year | 2012 |
| Journal | FEBS J | Volume | 279 |
| Issue | 22 | Pages | 4131-44 |
| PubMed ID | 22978324 | Mgi Jnum | J:201389 |
| Mgi Id | MGI:5513089 | Doi | 10.1111/febs.12006 |
| Citation | Fratini F, et al. (2012) Phosphorylation on threonine 11 of beta-dystrobrevin alters its interaction with kinesin heavy chain. FEBS J 279(22):4131-44 |
| abstractText | Dystrobrevin family members (alpha and beta) are cytoplasmic components of the dystrophin-associated glycoprotein complex, a multimeric protein complex first isolated from skeletal muscle, which links the extracellular matrix to the actin cytoskeleton. Dystrobrevin shares high homology with the cysteine-rich and C-terminal domains of dystrophin and a common domain organization. The beta-dystrobrevin isoform is restricted to nonmuscle tissues, serves as a scaffold for signaling complexes, and may participate in intracellular transport through its interaction with kinesin heavy chain. We have previously characterized the molecular determinants affecting the beta-dystrobrevin-kinesin heavy chain interaction, among which is cAMP-dependent protein kinase [protein kinase A (PKA)] phosphorylation of beta-dystrobrevin. In this study, we have identified beta-dystrobrevin residues phosphorylated in vitro by PKA with pull-down assays, surface plasmon resonance measurements, and MS analysis. Among the identified phosphorylated residues, we demonstrated, by site-directed mutagenesis, that Thr11 is the regulatory site for the beta-dystrobrevin-kinesin interaction. As dystrobrevin may function as a signaling scaffold for kinases/phosphatases, we also investigated whether beta-dystrobrevin is phosphorylated in vitro by kinases other than PKA. Thr11 was phosphorylated by protein kinase C, suggesting that this represents a key residue modified by the activation of different signaling pathways. |
