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- Title
Phosphorylation on threonine 11 of β-dystrobrevin alters its interaction with kinesin heavy chain.
- Authors
Fratini, Federica; Macchia, Gianfranco; Torreri, Paola; Matteucci, Andrea; Salzano, Anna Maria; Crescenzi, Marco; Macioce, Pompeo; Petrucci, Tamara C; Ceccarini, Marina
- Abstract
Dystrobrevin family members (α and β) 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 β-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 β-dystrobrevin-kinesin heavy chain interaction, among which is cAMP-dependent protein kinase [protein kinase A (PKA)] phosphorylation of β-dystrobrevin. In this study, we have identified β-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 β-dystrobrevin-kinesin interaction. As dystrobrevin may function as a signaling scaffold for kinases/phosphatases, we also investigated whether β-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.
- Publication
The FEBS journal, 2012, Vol 279, Issue 22, p4131
- ISSN
1742-4658
- Publication type
Journal Article
- DOI
10.1111/febs.12006