A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl.
The evolutionarily conserved proteins Par-6, atypical protein kinase C (aPKC), Cdc42 and Par-3 associate to regulate cell polarity and asymmetric cell division, but the downstream targets of this complex are largely unknown. Here we identify direct physiological interactions between mammalian aPKC, murine Par-6C (mPar-6C) and Mlgl, the mammalian orthologue of the Drosophila melanogaster tumour suppressor Lethal (2) giant larvae. In cultured cell lines and in mouse brain, aPKC, mPar-6C and Mlgl form a multiprotein complex in which Mlgl is targeted for phosphorylation on conserved serine residues. These phosphorylation sites are important for embryonic fibroblasts to polarize correctly in response to wounding and may regulate the ability of Mlgl to direct protein trafficking. Our data provide a direct physical and regulatory link between proteins of distinct polarity complexes, identify Mlgl as a functional substrate for aPKC in cell polarization and indicate that aPKC is directed to cell polarity substrates through a network of protein-protein interactions.
Plant
Pamela J
PJ
Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto M5G 1X5 Canada.
Fawcett
James P
JP
Lin
Dan C C
DC
Holdorf
Amy D
AD
Binns
Kathleen
K
Kulkarni
Sarang
S
Pawson
Tony
T
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001921:Brain / Q000201:enzymology; D019556:COS Cells; D016764:Cell Polarity / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000201:enzymology*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D046912:Multiprotein Complexes; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D014945:Wound Healing / Q000502:physiology; D000099221:Protein Kinase C zeta
D029721:Drosophila Proteins; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D020033:Protein Isoforms; D011493:Protein Kinase C; D011506:Proteins; D025521:Tumor Suppressor Proteins; D000099221:Protein Kinase C zeta; C081435:l(2)gl protein, Drosophila; C115015:PKC-3 protein