Atypical PKC phosphorylates microtubule affinity-regulating kinase 4 in vitro.
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.
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Farha
F
Naz
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Asimul
A
Islam
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India.
Faizan
F
Ahmad
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi, 110025, India. mihassan@jmi.ac.in.
Md Imtaiyaz
http://orcid.org/0000-0002-3663-4940
MI
Hassan
D000255:Adenosine Triphosphate / Q000378:metabolism; D016764:Cell Polarity; D006801:Humans; D006868:Hydrolysis; D009154:Mutation; D010766:Phosphorylation; D015202:Protein Engineering; D054730:Protein Interaction Domains and Motifs; D011493:Protein Kinase C / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine; D015398:Signal Transduction; D013379:Substrate Specificity; D013912:Threonine
D011994:Recombinant Proteins; D013912:Threonine; D012694:Serine; D000255:Adenosine Triphosphate; C483047:MARK4 protein, human; D017346:Protein Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C
ATP; Atypical protein kinase C; Cell polarity; Microtubule affinity-regulating kinase; Microtubule dynamics; Par-1