Into the Fold: Advances in Understanding APKC Membrane Dynamics

Overview

Journal Biochem J

Specialty Biochemistry

Date 2023 Dec 15

PMID 38100320

Authors

Mathias Cobbaut

Peter J Parker

Neil Q McDonald

Affiliations

Soon will be listed here.

Abstract

Atypical protein kinase Cs (aPKCs) are part of the PKC family of protein kinases and are atypical because they don't respond to the canonical PKC activators diacylglycerol (DAG) and Ca2+. They are central to the organization of polarized cells and are deregulated in several cancers. aPKC recruitment to the plasma membrane compartment is crucial to their encounter with substrates associated with polarizing functions. However, in contrast with other PKCs, the mechanism by which atypical PKCs are recruited there has remained elusive until recently. Here, we bring aPKC into the fold, summarizing recent reports on the direct recruitment of aPKC to membranes, providing insight into seemingly discrepant findings and integrating them with existing literature.

References

Kajimoto T, Caliman A, Tobias I, Okada T, Pilo C, Van A . Activation of atypical protein kinase C by sphingosine 1-phosphate revealed by an aPKC-specific activity reporter. Sci Signal. 2019; 12(562). PMC: 6657501. DOI: 10.1126/scisignal.aat6662. View

Lopez-Garcia L, Schulze J, Frohner W, Zhang H, Suss E, Weber N . Allosteric regulation of protein kinase PKCζ by the N-terminal C1 domain and small compounds to the PIF-pocket. Chem Biol. 2011; 18(11):1463-73. DOI: 10.1016/j.chembiol.2011.08.010. View

Wodarz A, Ramrath A, Grimm A, Knust E . Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol. 2000; 150(6):1361-74. PMC: 2150710. DOI: 10.1083/jcb.150.6.1361. View

Wang G, Krishnamurthy K, Umapathy N, Verin A, Bieberich E . The carboxyl-terminal domain of atypical protein kinase Czeta binds to ceramide and regulates junction formation in epithelial cells. J Biol Chem. 2009; 284(21):14469-75. PMC: 2682895. DOI: 10.1074/jbc.M808909200. View

Yamanaka T, Horikoshi Y, Sugiyama Y, Ishiyama C, Suzuki A, Hirose T . Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr Biol. 2003; 13(9):734-43. DOI: 10.1016/s0960-9822(03)00244-6. View

Jones K, Drummond M, Penkert R, Prehoda K . Cooperative regulation of C1-domain membrane recruitment polarizes atypical protein kinase C. J Cell Biol. 2023; 222(10). PMC: 10435729. DOI: 10.1083/jcb.202112143. View

Graybill C, Wee B, Atwood S, Prehoda K . Partitioning-defective protein 6 (Par-6) activates atypical protein kinase C (aPKC) by pseudosubstrate displacement. J Biol Chem. 2012; 287(25):21003-11. PMC: 3375524. DOI: 10.1074/jbc.M112.360495. View

Nakanishi H, Brewer K, EXTON J . Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1993; 268(1):13-6. View

Elbediwy A, Zhang Y, Cobbaut M, Riou P, Tan R, Roberts S . The Rho family GEF FARP2 is activated by aPKCι to control tight junction formation and polarity. J Cell Sci. 2019; 132(8). PMC: 6503954. DOI: 10.1242/jcs.223743. View

10.

Katti S, Krieger I, Ann J, Lee J, Sacchettini J, Igumenova T . Structural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists. Nat Commun. 2022; 13(1):2695. PMC: 9110374. DOI: 10.1038/s41467-022-30389-2. View

11.

Nunbhakdi-Craig V, Machleidt T, Ogris E, Bellotto D, White 3rd C, Sontag E . Protein phosphatase 2A associates with and regulates atypical PKC and the epithelial tight junction complex. J Cell Biol. 2002; 158(5):967-78. PMC: 2173154. DOI: 10.1083/jcb.200206114. View

12.

Wang Y, Seibenhener M, Vandenplas M, Wooten M . Atypical PKC zeta is activated by ceramide, resulting in coactivation of NF-kappaB/JNK kinase and cell survival. J Neurosci Res. 1999; 55(3):293-302. DOI: 10.1002/(SICI)1097-4547(19990201)55:3<293::AID-JNR4>3.0.CO;2-9. View

13.

Zhang H, Neimanis S, Lopez-Garcia L, Arencibia J, Amon S, Stroba A . Molecular mechanism of regulation of the atypical protein kinase C by N-terminal domains and an allosteric small compound. Chem Biol. 2014; 21(6):754-65. DOI: 10.1016/j.chembiol.2014.04.007. View

14.

Rodriguez J, Peglion F, Martin J, Hubatsch L, Reich J, Hirani N . aPKC Cycles between Functionally Distinct PAR Protein Assemblies to Drive Cell Polarity. Dev Cell. 2017; 42(4):400-415.e9. PMC: 5563072. DOI: 10.1016/j.devcel.2017.07.007. View

15.

Scotti M, Bamlet W, Smyrk T, Fields A, Murray N . Protein kinase Ciota is required for pancreatic cancer cell transformed growth and tumorigenesis. Cancer Res. 2010; 70(5):2064-74. PMC: 2881466. DOI: 10.1158/0008-5472.CAN-09-2684. View

16.

Hornbeck P, Zhang B, Murray B, Kornhauser J, Latham V, Skrzypek E . PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2014; 43(Database issue):D512-20. PMC: 4383998. DOI: 10.1093/nar/gku1267. View

17.

Parker P, Brown S, Calleja V, Chakravarty P, Cobbaut M, Linch M . Equivocal, explicit and emergent actions of PKC isoforms in cancer. Nat Rev Cancer. 2020; 21(1):51-63. DOI: 10.1038/s41568-020-00310-4. View

18.

Pu Y, Peach M, Garfield S, Wincovitch S, Marquez V, Blumberg P . Effects on ligand interaction and membrane translocation of the positively charged arginine residues situated along the C1 domain binding cleft in the atypical protein kinase C isoforms. J Biol Chem. 2006; 281(44):33773-88. DOI: 10.1074/jbc.M606560200. View

19.

Ways D, Cook P, Webster C, Parker P . Effect of phorbol esters on protein kinase C-zeta. J Biol Chem. 1992; 267(7):4799-805. View

20.

Mosior M, McLaughlin S . Peptides that mimic the pseudosubstrate region of protein kinase C bind to acidic lipids in membranes. Biophys J. 1991; 60(1):149-59. PMC: 1260046. DOI: 10.1016/S0006-3495(91)82038-0. View