Biology:PRKAR1A
 Generic protein structure example |
cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene.[1]
Function
cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed.[2]
Clinical significance
Functional null mutations in this gene cause Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome. This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2.[2]
Mutation of PRKAR1A leads to the Carney complex, associating multiple endocrine tumors.[citation needed]
Interactions
PRKAR1A has been shown to interact with:
- AKAP10,[3][4]
- AKAP1,[5][6]
- AKAP4,[7][8]
- ARFGEF1,[9]
- ARFGEF2,[9]
- Grb2,[10]
- MYO7A,[11]
- PRKAR1B,[5][12] and
- UBE2M.[13]
See also
- cAMP-dependent protein kinase
References
- ↑ "Exclusion of catalytic and regulatory subunits of cAMP-dependent protein kinase as candidate genes for the defect causing cystic fibrosis". Am J Hum Genet 41 (5): 925–32. December 1987. PMID 3479018.
- ↑ 2.0 2.1 "Entrez Gene: PRKAR1A protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5573.
- ↑ "D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain". Proc. Natl. Acad. Sci. U.S.A. 94 (21): 11184–9. October 1997. doi:10.1073/pnas.94.21.11184. PMID 9326583. Bibcode: 1997PNAS...9411184J.
- ↑ "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- ↑ 5.0 5.1 "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase a in vivo by the yeast two hybrid system". J. Mol. Biol. 327 (3): 609–18. March 2003. doi:10.1016/s0022-2836(03)00093-7. PMID 12634056.
- ↑ "Analysis of A-kinase anchoring protein (AKAP) interaction with protein kinase A (PKA) regulatory subunits: PKA isoform specificity in AKAP binding". J. Mol. Biol. 298 (2): 329–39. April 2000. doi:10.1006/jmbi.2000.3662. PMID 10764601.
- ↑ "A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum". Biol. Reprod. 68 (6): 2241–8. June 2003. doi:10.1095/biolreprod.102.013466. PMID 12606363.
- ↑ "Identification of tethering domains for protein kinase A type Ialpha regulatory subunits on sperm fibrous sheath protein FSC1". J. Biol. Chem. 273 (51): 34384–90. December 1998. doi:10.1074/jbc.273.51.34384. PMID 9852104.
- ↑ 9.0 9.1 "Protein kinase A-anchoring (AKAP) domains in brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2)". Proc. Natl. Acad. Sci. U.S.A. 100 (4): 1627–32. February 2003. doi:10.1073/pnas.0337678100. PMID 12571360. Bibcode: 2003PNAS..100.1627L.
- ↑ "The RIalpha subunit of protein kinase A (PKA) binds to Grb2 and allows PKA interaction with the activated EGF-receptor". Oncogene 14 (8): 923–8. February 1997. doi:10.1038/sj.onc.1200906. PMID 9050991.
- ↑ "Unconventional myosin VIIA is a novel A-kinase-anchoring protein". J. Biol. Chem. 275 (38): 29654–9. September 2000. doi:10.1074/jbc.M004393200. PMID 10889203.
- ↑ "Novel isozymes of cAMP-dependent protein kinase exist in human cells due to formation of RI alpha-RI beta heterodimeric complexes". J. Biol. Chem. 268 (28): 21276–83. October 1993. doi:10.1016/S0021-9258(19)36921-2. PMID 8407966.
- ↑ "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. 2007. doi:10.1038/msb4100134. PMID 17353931.
Further reading
- "Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit (PRKAR1A) in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas" (Carney complex)". Ann. N. Y. Acad. Sci. 968 (1): 3–21. 2002. doi:10.1111/j.1749-6632.2002.tb04323.x. PMID 12119264. Bibcode: 2002NYASA.968....3S.
- "Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease". Ann. N. Y. Acad. Sci. 968 (1): 240–55. 2002. doi:10.1111/j.1749-6632.2002.tb04339.x. PMID 12119280. Bibcode: 2002NYASA.968..240B.
- "Intracellular targeting of protein kinases and phosphatases". Diabetes 51 (Suppl 3): S385–8. 2003. doi:10.2337/diabetes.51.2007.s385. PMID 12475780.
- "Human tumors associated with Carney complex and germline PRKAR1A mutations: a protein kinase A disease!". FEBS Lett. 546 (1): 59–64. 2003. doi:10.1016/S0014-5793(03)00452-6. PMID 12829237.
- "Minireview: PRKAR1A: normal and abnormal functions". Endocrinology 145 (12): 5452–8. 2004. doi:10.1210/en.2004-0900. PMID 15331577.
- "Tumor reversion: protein kinase A isozyme switching". Ann. N. Y. Acad. Sci. 1058: 76–86. 2006. doi:10.1196/annals.1359.014. PMID 16394127. https://zenodo.org/record/1235884.
- "Growth hormone-secreting tumors: genetic aspects and data from animal models". Neuroendocrinology 83 (3–4): 166–78. 2006. doi:10.1159/000095525. PMID 17047380.
- "Will diverse Tat interactions lead to novel antiretroviral drug targets?". Current Drug Targets 7 (12): 1595–606. 2007. doi:10.2174/138945006779025338. PMID 17168834.
- "The tissue-specific extinguisher locus TSE1 encodes a regulatory subunit of cAMP-dependent protein kinase". Cell 66 (5): 849–59. 1991. doi:10.1016/0092-8674(91)90432-X. PMID 1832337. https://epub.ub.uni-muenchen.de/3205/1/010.pdf.
- "Subtractive hybridization cloning of a tissue-specific extinguisher: TSE1 encodes a regulatory subunit of protein kinase A". Cell 66 (5): 861–72. 1991. doi:10.1016/0092-8674(91)90433-Y. PMID 1889088.
- "HIV inhibits the early steps of lymphocyte activation, including initiation of inositol phospholipid metabolism". J. Immunol. 145 (11): 3699–705. 1991. doi:10.4049/jimmunol.145.11.3699. PMID 1978848.
- "The two mRNA forms for the type I alpha regulatory subunit of cAMP-dependent protein kinase from human testis are due to the use of different polyadenylation site signals". Biochem. Biophys. Res. Commun. 167 (1): 323–30. 1990. doi:10.1016/0006-291X(90)91768-N. PMID 2310396.
- "Coordinate regulation of two genes encoding gluconeogenic enzymes by the trans-dominant locus Tse-1". Proc. Natl. Acad. Sci. U.S.A. 85 (19): 7302–6. 1988. doi:10.1073/pnas.85.19.7302. PMID 2902627. Bibcode: 1988PNAS...85.7302L.
- "Molecular cloning, cDNA structure and deduced amino acid sequence for a type I regulatory subunit of cAMP-dependent protein kinase from human testis". Biochem. Biophys. Res. Commun. 149 (3): 939–45. 1988. doi:10.1016/0006-291X(87)90499-2. PMID 3426618.
- "Phosphorylation of cAMP-dependent protein kinase subunits". Adv. Enzyme Regul. 20: 195–209. 1982. doi:10.1016/0065-2571(82)90016-4. PMID 6287816.
- "HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of phosphorylation and segmentation in class i major histocompatibility complex gene structure". J. Biol. Chem. 259 (21): 13504–10. 1984. doi:10.1016/S0021-9258(18)90722-2. PMID 6333425.
- "Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A". Mol. Cell. Biol. 13 (1): 358–66. 1993. doi:10.1128/MCB.13.1.358. PMID 7678053.
- "Human immunodeficiency virus proteins induce the inhibitory cAMP/protein kinase A pathway in normal lymphocytes". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6676–80. 1993. doi:10.1073/pnas.90.14.6676. PMID 7688126. Bibcode: 1993PNAS...90.6676H.
- "HIV Gag p17 protein impairs proliferation of normal lymphocytes in vitro". AIDS 8 (7): 1016–7. 1994. doi:10.1097/00002030-199407000-00025. PMID 7946090.
External links
- PDBe-KB provides an overview of all the structure information available in the PDB for Human cAMP-dependent protein kinase type I-alpha regulatory subunit (PRKAR1A)
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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