Biology:AKAP13
 Generic protein structure example |
A-kinase anchor protein 13 is a protein that in humans is encoded by the AKAP13 gene.[1][2][3] This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.
Function
A-kinase anchor protein 13/Rho guanine nucleotide exchange factor 13 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein.[4][5] Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as AKAP13, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions.[6] In particular, active Rho is a major regulator of the cell actin cytoskeleton.[6]
AKAP13 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins.[4][5] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF), and ARHGEF12 (also known as LARG). [7][4] GPCR-regulated AKAP13 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. Unlike the other three members, AKAP13 does not function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins.[8]
The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins that have the common function of binding to the regulatory subunit of protein kinase A (PKA), thus confining the holoenzyme to discrete locations within the cell. The AKAP13 gene encodes a member of the AKAP family since the protein binds tightly to PKA, especially in the heart.
Alternative splicing of this gene results in at least 3 transcript variants encoding different isoforms. All three contain the Dbl oncogene homology (DH) domain plus Pleckstrin homology (PH) domain (DH/PH domain) characteristic of Rho family GEFs, while only the longer two isoforms also contain the AKAP domain.[3] Therefore, these isoforms may function as scaffolding proteins to coordinate Rho signaling and protein kinase A signaling.
Interactions
AKAP13 has been shown to interact with:
See also
- Second messenger system
- G protein-coupled receptor
- Heterotrimeric G protein
- Small GTPases
- Rho family of GTPases
- Protein kinase A
References
- ↑ 1.0 1.1 "Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action". Oncogene 16 (19): 2513–26. May 1998. doi:10.1038/sj.onc.1201783. PMID 9627117.
- ↑ "Interaction of the regulatory subunit (RII) of cAMP-dependent protein kinase with RII-anchoring proteins occurs through an amphipathic helix binding motif". The Journal of Biological Chemistry 266 (22): 14188–92. August 1991. doi:10.1016/S0021-9258(18)98665-5. PMID 1860836.
- ↑ 3.0 3.1 "Entrez Gene: AKAP13 A kinase (PRKA) anchor protein 13". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=11214.
- ↑ 4.0 4.1 4.2 "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". The Journal of Biological Chemistry 276 (47): 44247–57. November 2001. doi:10.1074/jbc.M106629200. PMID 11546812.
- ↑ 5.0 5.1 5.2 5.3 "Role of Lbc RhoGEF in Galpha12/13-induced signals to Rho GTPase". Cellular Signalling 16 (2): 201–9. February 2004. doi:10.1016/S0898-6568(03)00132-3. PMID 14636890.
- ↑ 6.0 6.1 "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology 92 (10–11): 303–15. Oct–Nov 2013. doi:10.1016/j.ejcb.2013.09.002. PMID 24183240.
- ↑ "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?". Oncogene 20 (13): 1661–8. March 2001. doi:10.1038/sj.onc.1204182. PMID 11313914.
- ↑ "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences 68 (19–20): 2309–17. April 2001. doi:10.1016/S0024-3205(01)01020-7. PMID 11358341.
- ↑ "Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation". The Journal of Biological Chemistry 277 (47): 45361–70. November 2002. doi:10.1074/jbc.M202447200. PMID 12270917.
- ↑ "Bioinformatic design of A-kinase anchoring protein-in silico: a potent and selective peptide antagonist of type II protein kinase A anchoring". Proceedings of the National Academy of Sciences of the United States of America 100 (8): 4445–50. April 2003. doi:10.1073/pnas.0330734100. PMID 12672969. Bibcode: 2003PNAS..100.4445A.
- ↑ "Association of the type II cAMP-dependent protein kinase with a human thyroid RII-anchoring protein. Cloning and characterization of the RII-binding domain". The Journal of Biological Chemistry 267 (19): 13376–82. July 1992. doi:10.1016/S0021-9258(18)42221-1. PMID 1618839.
External links
- Human AKAP13 genome location and AKAP13 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q12802 (A-kinase anchor protein 13) at the PDBe-KB.
Further reading
- "Type II regulatory subunit (RII) of the cAMP-dependent protein kinase interaction with A-kinase anchor proteins requires isoleucines 3 and 5". The Journal of Biological Chemistry 269 (39): 24245–51. September 1994. doi:10.1016/S0021-9258(19)51074-2. PMID 7929081.
- "Novel human oncogene lbc detected by transfection with distinct homology regions to signal transduction products". Oncogene 9 (2): 621–8. February 1994. PMID 8290273.
- "Activation of the Lbc Rho exchange factor proto-oncogene by truncation of an extended C terminus that regulates transformation and targeting". Molecular and Cellular Biology 19 (2): 1334–45. February 1999. doi:10.1128/mcb.19.2.1334. PMID 9891067.
- "Physical and functional interactions of Galphaq with Rho and its exchange factors". The Journal of Biological Chemistry 276 (18): 15445–52. May 2001. doi:10.1074/jbc.M008961200. PMID 11278452.
- "A novel mechanism of PKA anchoring revealed by solution structures of anchoring complexes". The EMBO Journal 20 (7): 1651–62. April 2001. doi:10.1093/emboj/20.7.1651. PMID 11285229.
- "The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway". The Journal of Biological Chemistry 276 (50): 46792–7. December 2001. doi:10.1074/jbc.M106927200. PMID 11579095.
- "Ht31: the first protein kinase A anchoring protein to integrate protein kinase A and Rho signaling". FEBS Letters 507 (3): 264–8. November 2001. doi:10.1016/S0014-5793(01)02995-7. PMID 11696353.
- "Characterization of the interactions between the small GTPase RhoA and its guanine nucleotide exchange factors". Analytical Biochemistry 310 (2): 156–62. November 2002. doi:10.1016/S0003-2697(02)00382-2. PMID 12423633.
- "The minor histocompatibility antigen HA-3 arises from differential proteasome-mediated cleavage of the lymphoid blast crisis (Lbc) oncoprotein". Blood 102 (2): 621–9. July 2003. doi:10.1182/blood-2003-01-0260. PMID 12663445.
- "Muscle-type creatine kinase interacts with central domains of the M-band proteins myomesin and M-protein". Journal of Molecular Biology 332 (4): 877–87. September 2003. doi:10.1016/S0022-2836(03)00921-5. PMID 12972258.
- "A Rho exchange factor mediates fMet-Leu-Phe-induced NF-kappaB activation in human peripheral blood monocytes". The Journal of Biological Chemistry 279 (8): 7208–12. February 2004. doi:10.1074/jbc.M309542200. PMID 14660653.
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