Physiologic and Pathophysiologic Roles of AKAP12

Overview

Journal Sci Prog

Publisher Sage Publications

Specialty Science

Date 2022 Jul 1

PMID 35775596

Authors

Hui Li

Affiliations

Soon will be listed here.

Abstract

A kinase anchoring protein (AKAP) 12 is a scaffolding protein that improves the specificity and efficiency of spatiotemporal signal through assembling intracellular signal proteins into a specific complex. AKAP12 is a negative mitogenic regulator that plays an important role in controlling cytoskeletal architecture, maintaining endothelial integrity, regulating glial function and forming blood-brain barrier (BBB) and blood retinal barrier (BRB). Moreover, elevated or reduced AKAP12 contributes to a variety of diseases. Complex connections between AKAP12 and various diseases including chronic liver diseases (CLDs), inflammatory diseases and a series of cancers will be tried to delineate in this paper. We first describe the expression, distribution and physiological function of AKAP12. Then we summarize the current knowledge of different connections between AKAP12 expression and various diseases. Some research groups have found paradoxical roles of AKAP12 in different diseases and further confirmation is needed. This paper aims to assess the role of AKAP12 in physiology and diseases to help lay the foundation for the design of small molecules for specific AKAP12 to correct the pathological signal defects.

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References

Fonseca-Camarillo G, Furuzawa-Carballeda J, Priego-Ranero A, Zuniga R, Martinez-Benitez B, Yamamoto-Furusho J . AKAP12/Gravin is over-expressed in patients with ulcerative colitis. Immunol Res. 2021; 69(5):429-435. DOI: 10.1007/s12026-021-09214-3. View

Qasim H, McConnell B . AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems. J Am Heart Assoc. 2020; 9(13):e016615. PMC: 7670535. DOI: 10.1161/JAHA.120.016615. View

Adluri R, Thirunavukkarasu M, Zhan L, Akita Y, Samuel S, Otani H . Thioredoxin 1 enhances neovascularization and reduces ventricular remodeling during chronic myocardial infarction: a study using thioredoxin 1 transgenic mice. J Mol Cell Cardiol. 2010; 50(1):239-47. PMC: 3397477. DOI: 10.1016/j.yjmcc.2010.11.002. View

Barnett M, Madgwick D, Takemoto D . Protein kinase C as a stress sensor. Cell Signal. 2007; 19(9):1820-9. PMC: 1986756. DOI: 10.1016/j.cellsig.2007.05.014. View

Akakura S, Nochajski P, Gao L, Sotomayor P, Matsui S, Gelman I . Rb-dependent cellular senescence, multinucleation and susceptibility to oncogenic transformation through PKC scaffolding by SSeCKS/AKAP12. Cell Cycle. 2010; 9(23):4656-65. PMC: 3048035. DOI: 10.4161/cc.9.23.13974. View

Boultwood J, Pellagatti A, Watkins F, Campbell L, Esoof N, Cross N . Low expression of the putative tumour suppressor gene gravin in chronic myeloid leukaemia, myelodysplastic syndromes and acute myeloid leukaemia. Br J Haematol. 2004; 126(4):508-11. DOI: 10.1111/j.1365-2141.2004.05067.x. View

Shih M, Lin F, Scott J, Wang H, Malbon C . Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin. J Biol Chem. 1999; 274(3):1588-95. DOI: 10.1074/jbc.274.3.1588. View

Ramani K, Tomasi M, Berlind J, Mavila N, Sun Z . Role of A-Kinase Anchoring Protein Phosphorylation in Alcohol-Induced Liver Injury and Hepatic Stellate Cell Activation. Am J Pathol. 2018; 188(3):640-655. PMC: 5842034. DOI: 10.1016/j.ajpath.2017.11.017. View

Xia W, Unger P, Miller L, Nelson J, Gelman I . The Src-suppressed C kinase substrate, SSeCKS, is a potential metastasis inhibitor in prostate cancer. Cancer Res. 2001; 61(14):5644-51. View

10.

Wong W, Scott J . AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol. 2004; 5(12):959-70. DOI: 10.1038/nrm1527. View

11.

Hehnly H, Canton D, Bucko P, Langeberg L, Ogier L, Gelman I . A mitotic kinase scaffold depleted in testicular seminomas impacts spindle orientation in germ line stem cells. Elife. 2015; 4:e09384. PMC: 4612572. DOI: 10.7554/eLife.09384. View

12.

Diviani D, Scott J . AKAP signaling complexes at the cytoskeleton. J Cell Sci. 2001; 114(Pt 8):1431-7. DOI: 10.1242/jcs.114.8.1431. View

13.

Benz P, Ding Y, Stingl H, Loot A, Zink J, Wittig I . AKAP12 deficiency impairs VEGF-induced endothelial cell migration and sprouting. Acta Physiol (Oxf). 2019; 228(1):e13325. PMC: 6916389. DOI: 10.1111/apha.13325. View

14.

Fan Q, Yin X, Rababah A, Diaz Diaz A, Wijaya C, Singh S . Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis. Am J Physiol Heart Circ Physiol. 2019; 317(4):H793-H810. PMC: 6843010. DOI: 10.1152/ajpheart.00215.2019. View

15.

Coats S, Covington J, Su M, Eren M, Hao Q, Vaughan D . SSeCKS gene expression in vascular smooth muscle cells: regulation by angiotensin II and a potential role in the regulation of PAI-1 gene expression. J Mol Cell Cardiol. 2000; 32(12):2207-19. DOI: 10.1006/jmcc.2000.1246. View

16.

Bateman N, Jaworski E, Ao W, Wang G, Litzi T, Dubil E . Elevated AKAP12 in paclitaxel-resistant serous ovarian cancer cells is prognostic and predictive of poor survival in patients. J Proteome Res. 2015; 14(4):1900-10. PMC: 4612617. DOI: 10.1021/pr5012894. View

17.

Xie W, Su W, Zhang L, Shang Q, Su B . SSeCKS/AKAP12 induces repulsion between human prostate cancer and microvessel endothelial cells through the activation of Semaphorin 3F. Biochem Biophys Res Commun. 2017; 490(4):1394-1398. DOI: 10.1016/j.bbrc.2017.07.043. View

18.

Gerthoffer W . Actin cytoskeletal dynamics in smooth muscle contraction. Can J Physiol Pharmacol. 2005; 83(10):851-6. DOI: 10.1139/y05-088. View

19.

Jiang W, Song L, Shao J, Wang L, Lu J, Liu H . [The role of hepatic stellate cells SSeCKS expression in liver fibrosis]. Zhonghua Nei Ke Za Zhi. 2008; 47(7):570-3. View

20.

Muramatsu M, Akakura S, Gao L, Peresie J, Balderman B, Gelman I . SSeCKS/Akap12 suppresses metastatic melanoma lung colonization by attenuating Src-mediated pre-metastatic niche crosstalk. Oncotarget. 2018; 9(71):33515-33527. PMC: 6173366. DOI: 10.18632/oncotarget.26067. View