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Protein kinase A regulates AKAP250 (gravin) scaffold binding to the β 2 ‐adrenergic receptor
Author(s) -
Tao Jiangchuan,
Wang Hsienyu,
Malbon Craig C.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg628
Subject(s) - scaffold protein , biology , microbiology and biotechnology , protein kinase a , phosphorylation , receptor , interleukin 13 receptor , enzyme linked receptor , biochemistry , signal transduction , insulin like growth factor 1 receptor , growth factor
A‐kinase‐anchoring protein 250 (AKAP250; gravin) acts as a scaffold that binds protein kinase A (PKA), protein kinase C and protein phosphatases, associating reversibly with the β 2 ‐adrenergic receptor. The receptor‐binding domain of the scaffold and the regulation of the receptor–scaffold association was revealed through mutagenesis and biochemical analyses. The AKAP domain found in other members of this superfamily is essential for the scaffold–receptor interactions. Gravin constructs lacking the AKAP domain displayed no binding to the receptor. Metabolic labeling studies in vivo demonstrate agonist‐stimulated phosphorylation of gravin and enhanced gravin–receptor association. Analysis of the AKAP domain revealed two canonical PKA sites phosphorylated in response to elevated cAMP, blocked by PKA inhibitor, and essential for scaffold–receptor association and for resensitization of the receptor. The AKAP appears to provide the catalytic PKA activity responsible for phosphorylation of the scaffold in response to agonist activation of the receptor as well as for the association of the scaffold with the receptor, a step critical to receptor resensitization.