Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs.
The Par polarity complex creates mutually exclusive cortical domains in diverse animal cells. Activity of the atypical protein kinase C (aPKC) is a key output of the Par complex as phosphorylation removes substrates from the Par domain. Here, we investigate how diverse, apparently unrelated Par substrates couple phosphorylation to cortical displacement. Each protein contains a basic and hydrophobic (BH) motif that interacts directly with phospholipids and also overlaps with aPKC phosphorylation sites. Phosphorylation alters the electrostatic character of the sequence, inhibiting interaction with phospholipids and the cell cortex. We searched for overlapping BH and aPKC phosphorylation site motifs (i.e., putative phosphoregulated BH motifs) in several animal proteomes. Candidate proteins with strong PRBH signals associated with the cell cortex but were displaced into the cytoplasm by aPKC. These findings demonstrate a potentially general mechanism for exclusion of proteins from the Par cortical domain in polarized cells.
Department of Chemistry and Biochemistry, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA.
Matthew J
MJ
Bailey
Department of Chemistry and Biochemistry, Institute of Molecular Biology, University of Oregon, Eugene, OR 97403, USA. Electronic address: prehoda@uoregon.edu.
Kenneth E
KE
Prehoda
D020816:Amino Acid Motifs / Q000235:genetics*; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000235:genetics
D050976:Basic-Leucine Zipper Transcription Factors; D029721:Drosophila Proteins; C109768:PDP1 protein, Drosophila; D010743:Phospholipids; D020543:Proteome; C115015:PKC-3 protein; D011493:Protein Kinase C