AKAP12 explained
A-kinase anchor protein 12, aka AKAP250, is an enzyme that in humans is encoded by the AKAP12 gene.[1] [2]
Function
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinase A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms.[2]
Interactions
AKAP12 has been shown to interact with Beta-2 adrenergic receptor.[3] [4]
Further reading
- Lester LB, Scott JD . Anchoring and scaffold proteins for kinases and phosphatases . Recent Prog. Horm. Res. . 52 . 409–29; discussion 429–30 . 1997 . 9238861 .
- Michel JJ, Scott JD . AKAP mediated signal transduction . Annu. Rev. Pharmacol. Toxicol. . 42 . 235–57 . 2002 . 11807172 . 10.1146/annurev.pharmtox.42.083101.135801 .
- Yildirim M, Paydas S, Tanriverdi K, Seydaoglu G, Disel U, Yavuz S . Gravin gene expression in acute leukaemias: clinical importance and review of the literature . Leuk. Lymphoma . 48 . 6 . 1167–72 . 2007 . 17577780 . 10.1080/10428190701377055 . 35975874 .
- Gordon T, Grove B, Loftus JC, O'Toole T, McMillan R, Lindstrom J, Ginsberg MH . Molecular cloning and preliminary characterization of a novel cytoplasmic antigen recognized by myasthenia gravis sera . J. Clin. Invest. . 90 . 3 . 992–9 . 1992 . 1522245 . 329955 . 10.1172/JCI115976 .
- Sato N, Kokame K, Shimokado K, Kato H, Miyata T . Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells: 12 up-regulated distinct genes including 5 cell growth-related, 3 thrombosis-related, and 4 others . J. Biochem. . 123 . 6 . 1119–26 . 1998 . 9604001 . 10.1093/oxfordjournals.jbchem.a022051 .
- Shih M, Lin F, Scott JD, Wang HY, Malbon CC . Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin . J. Biol. Chem. . 274 . 3 . 1588–95 . 1999 . 9880537 . 10.1074/jbc.274.3.1588 . free .
- Lin F, ((Wang Hy)), Malbon CC . Gravin-mediated formation of signaling complexes in beta 2-adrenergic receptor desensitization and resensitization . J. Biol. Chem. . 275 . 25 . 19025–34 . 2000 . 10858453 . 10.1074/jbc.275.25.19025 . free .
- Fan G, Shumay E, Wang H, Malbon CC . The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization . J. Biol. Chem. . 276 . 26 . 24005–14 . 2001 . 11309381 . 10.1074/jbc.M011199200 . free .
- Grove BD, Bruchey AK . Intracellular distribution of gravin, a PKA and PKC binding protein, in vascular endothelial cells . J. Vasc. Res. . 38 . 2 . 163–75 . 2001 . 11316952 . 10.1159/000051043 . 6002979 .
- Sasaki H, Kunimatsu M, Fujii Y, Yamakawa Y, Fukai I, Kiriyama M, Nonaka M, Sasaki M . Autoantibody to gravin is expressed more strongly in younger and nonthymomatous patients with myasthenia gravis . Surg. Today . 31 . 11 . 1036–7 . 2001 . 11766078 . 10.1007/s005950170020 . 22167880 .
- Piontek J, Brandt R . Differential and regulated binding of cAMP-dependent protein kinase and protein kinase C isoenzymes to gravin in human model neurons: Evidence that gravin provides a dynamic platform for the localization for kinases during neuronal development . J. Biol. Chem. . 278 . 40 . 38970–9 . 2003 . 12857743 . 10.1074/jbc.M306749200 . free .
- Tao J, Wang HY, Malbon CC . Protein kinase A regulates AKAP250 (gravin) scaffold binding to the beta2-adrenergic receptor . EMBO J. . 22 . 24 . 6419–29 . 2003 . 14657015 . 291823 . 10.1093/emboj/cdg628 .
- Choi MC, Jong HS, Kim TY, Song SH, Lee DS, Lee JW, Kim TY, Kim NK, Bang YJ . AKAP12/Gravin is inactivated by epigenetic mechanism in human gastric carcinoma and shows growth suppressor activity . Oncogene . 23 . 42 . 7095–103 . 2004 . 15258566 . 10.1038/sj.onc.1207932 . free .
- Ballif BA, Villén J, Beausoleil SA, Schwartz D, Gygi SP . Phosphoproteomic analysis of the developing mouse brain . Mol. Cell. Proteomics . 3 . 11 . 1093–101 . 2004 . 15345747 . 10.1074/mcp.M400085-MCP200 . free .
- Streb JW, Miano JM . AKAP12alpha, an atypical serum response factor-dependent target gene . J. Biol. Chem. . 280 . 6 . 4125–34 . 2005 . 15590635 . 10.1074/jbc.M412466200 . free .
- Streb JW, Miano JM . Cross-species sequence analysis reveals multiple charged residue-rich domains that regulate nuclear/cytoplasmic partitioning and membrane localization of a kinase anchoring protein 12 (SSeCKS/Gravin) . J. Biol. Chem. . 280 . 30 . 28007–14 . 2005 . 15923193 . 10.1074/jbc.M414017200 . free .
Notes and References
- Nauert JB, Klauck TM, Langeberg LK, Scott JD . Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein . Curr. Biol. . 7 . 1 . 52–62 . Mar 1997 . 9000000 . 10.1016/S0960-9822(06)00027-3 . 18843778 . free . 1997CBio....7...52N .
- Web site: Entrez Gene: AKAP12 A kinase (PRKA) anchor protein (gravin) 12.
- Fan G, Shumay E, Wang H, Malbon CC . The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization . J. Biol. Chem. . 276 . 26 . 24005–14 . Jun 2001 . 11309381 . 10.1074/jbc.M011199200 . free .
- Shih M, Lin F, Scott JD, Wang HY, Malbon CC . Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin . J. Biol. Chem. . 274 . 3 . 1588–95 . Jan 1999 . 9880537 . 10.1074/jbc.274.3.1588 . free .