MOJ
eISSN: 2374-6912
Submit manuscript...
Editorial Volume 3 Issue 4
Unfolding the role of PKC isoforms in intestinal physiology
Patrice G Bouyer,
Verify Captcha
Regret for the inconvenience: we are taking measures to prevent fraudulent form submissions by extractors and page crawlers. Please type the correct Captcha word to see email ID.
Natasa Petreska, Jesse Smallwood
Verify Captcha
Regret for the inconvenience: we are taking measures to prevent fraudulent form submissions by extractors and page crawlers. Please type the correct Captcha word to see email ID.
Department of Biology, Valparaiso University, USA
Correspondence: Patrice G Bouyer, Department of Biology, Valparaiso University, Neils Science Center, Valparaiso, USA, Tel 2194645487, Fax 2194645489
Received: July 18, 2016 | Published: August 2, 2016
Citation: Bouyer PG, Petreska N, Smallwood J. Unfolding the role of PKC isoforms in intestinal physiology. MOJ Cell Sci Rep. 2016;3(4):106. DOI: 10.15406/mojcsr.2016.03.00063
Editorial
The protein kinase C (PKC) family has twelve isoforms,1 and the number of biological events driven by PKC isoforms is expanding. Some of the pathways the PKCs are involved encompass, but not restricted to: cell division, migration, apoptosis, protein trafficking, regulation of ion transport and barrier function.1-3 Maintenance of intestinal barrier function is critical in order to preserve normal transepithelial transport as well as to prevent pathogens and toxins from entering the body.4 For instance, PKCα, PKCβII, PKCδ, PKCε or PKCh have been shown to modulate intestinal barrier integrity during inflammation or cell injury,3 by phosphorylating tight junction proteins or cytoskeleton proteins.3,4 Some of the previous mentioned PKC isoforms are also involved in the regulation of ion transport in the intestine. For example, PKCα is a well known regulator of the Na/H exchanger, which participates in NaCl absorption in the intestine.5 PKCε and PKCδ are implicated in the internalization of the Na-K-2Cl cotransporter 1, and thus decrease in fluid secretion in the colon.6 In addition PKCδ has been also suggested to decrease Cl− secretion in the colon by blocking the K+-channel KCNQ1.7
As mentioned, the same isoform can be involved in very different biological processes. Thus, one important question arising from these observations: How is the same isoform driving specifically different biological events? Specificity is conveyed by the spatio-temporal distribution of the isoform, which is dependent on the association of the isoform with specific binding proteins such as receptor activated C kinase, A kinase anchoring protein or annexins.8,9 The second mechanism being the target proteins phosphorylated by PKC isoform such as myristoylated, alanine rich C kinase substrate or adducin.9,10 To date the proteins implicated in the specificity of the PKC isoform in intestinal biology (e.g., ion transport, barrier function) remains elusive. Much work is need if we intend to understand how barrier function and ion transport are regulated by the PKC in normal and disease states in the intestine. Defining the scaffolding and target proteins of the PKC isoform may prove very useful targets to treat diseases such intestinal inflammation or cancer.11
Acknowledgements
None.
Conflict of interest
The author declares no conflict of interest.
References
- Steinberg SF. Structural basis of protein kinase C isoform function. Physiological reviews. 2008;88:1341–1378.
- Alvi F, Idkowiak Baldys J, Baldys A, et al. Regulation of membrane trafficking and endocytosis by protein kinase C: emerging role of the pericentrion, a novel protein kinase C–dependent subset of recycling endosomes. Cellular and Molecular Life Science. 2007;64:263–270.
- Farhadi A, Keshavarzian A, Ranjbaran Z, et al. The role of protein kinase C isoforms in modulating injury and repair of the intestinal barrier. The Journal of Pharmacology and Experimental Therapeutics. 2006;316:1–7.
- Shen L, Weber CR, Raleigh DR, et al. Tight junction pore and leak pathways: a dynamic duo. Annual Review of Physiology. 2011;73:283–309.
- Kato A, Romero MF. Regulation of electroneutral NaCl absorption by the small intestine. Annual Review of Physiology. 2011;73:261–281.
- Tang J, Bouyer P, Mykoniatis A, et al. Activated PKCδ and PKCε inhibit epithelial chloride secretion response to cAMP via inducing internalization of the Na+–K+–2Cl– cotransporter NKCC1. The Journal of Biological Chemistry. 2010;285:34072–34085.
- O'Mahony F, Alzamora R, Chung HL, et al. Genomic priming of the antisecretory response to estrogen in rat distal colon throughout the estrous cycle. Molecular Endocrinology. 2009;23:1885–1899.
- Hoque M, Rentero C, Cairns R, et al. Annexins – scaffolds modulating PKC localization and signaling. Cellular Signaling. 2014;26:1213–1225.
- Blackshear PJ. The MARCKS family of cellular protein kinase C substrates. The Journal of Biological Chemistry. 1993;268:1501–1504.
- Larsson C. Protein kinase C and the regulation of the actin cytoskeleton. Cellular Signaling. 2006;18:276–284.
- Kang JH, Toita R, Kim CW, et al. Protein kinase C (PKC) isozyme–specific substrates and their design. Biotechnology Advances. 2012;30:1662–1672.
©2016 Bouyer, et al. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially.