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Atypical PKC Phosphorylates Microtubule Affinity-regulating Kinase 4 in Vitro

Overview
Publisher Springer
Specialty Biochemistry
Date 2015 Sep 9
PMID 26346160
Citations 7
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Abstract

MAP/Microtubule affinity-regulating kinase 4 (MARK4), a Ser/Thr protein kinases, is related to the Par-1 (partitioning-defective) gene products, and is the human ortholog of Par-1. MARK4 shows its role in the cell polarity at the time of embryonic development. It is mostly located at the basal region of cells, providing apico-basal polarity. Here, we made two variants of human Par-1d (MARK4), kinase domain (MARK4-F2), and kinase domain along with 59 N-terminal residues (MARK4-F1) and saw their ATPase hydrolysis in the presence of each other. We observed that the activity of one variant was increased in the presence of other. We also demonstrated that both variants were phosphorylated by atypical PKC and their activities were increased in the presence of increasing concentration of atypical protein kinase c (aPKC). The phosphorylation was observed at the serine and threonine residues of MARK4. The interaction of MARK2 and MARK3 with aPKC and their negative regulation by aPKC is already known. This study confirms a functional link between aPKC and MARK4, two central determinants of cell polarity, and it suggests that aPKC may regulate all four members of Par-1 through phosphorylating them in polarized cells.

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References
1.
Inglis J, Lee M, Hill R . Emk, a protein kinase with homologs in yeast maps to mouse chromosome 19. Mamm Genome. 1993; 4(7):401-3. DOI: 10.1007/BF00360595. View

2.
Naz F, Singh P, Islam A, Ahmad F, Hassan M . Human microtubule affinity-regulating kinase 4 is stable at extremes of pH. J Biomol Struct Dyn. 2015; 34(6):1241-51. DOI: 10.1080/07391102.2015.1074942. View

3.
Lizcano J, Goransson O, Toth R, Deak M, Morrice N, Boudeau J . LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004; 23(4):833-43. PMC: 381014. DOI: 10.1038/sj.emboj.7600110. View

4.
Manning G, Whyte D, Martinez R, Hunter T, Sudarsanam S . The protein kinase complement of the human genome. Science. 2002; 298(5600):1912-34. DOI: 10.1126/science.1075762. View

5.
Hurov J, Stappenbeck T, Zmasek C, White L, Ranganath S, Russell J . Immune system dysfunction and autoimmune disease in mice lacking Emk (Par-1) protein kinase. Mol Cell Biol. 2001; 21(9):3206-19. PMC: 86958. DOI: 10.1128/MCB.21.9.3206-3219.2001. View