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MARK2/EMK1/Par-1Balpha phosphorylation of Rab11-family interacting protein 2 is necessary for the timely establishment of polarity in Madin-Darby canine kidney cells.

http://www.ncbi.nlm.nih.gov/pubmed/16775013

Rab11a, myosin Vb, and the Rab11-family interacting protein 2 (FIP2) regulate plasma membrane recycling in epithelial cells. This study sought to characterize more fully Rab11-FIP2 function by identifying kinase activities modifying Rab11-FIP2. We have found that gastric microsomal membrane extracts phosphorylate Rab11-FIP2 on serine 227. We identified the kinase that phosphorylated Rab11-FIP2 as MARK2/EMK1/Par-1Balpha (MARK2), and recombinant MARK2 phosphorylated Rab11-FIP2 only on serine 227. We created stable Madin-Darby canine kidney (MDCK) cell lines expressing enhanced green fluorescent protein-Rab11-FIP2 wild type or a nonphosphorylatable mutant [Rab11-FIP2(S227A)]. Analysis of these cell lines demonstrates a new role for Rab11-FIP2 in addition to that in the plasma membrane recycling system. In calcium switch assays, cells expressing Rab11-FIP2(S227A) showed a defect in the timely reestablishment of p120-containing junctional complexes. However, Rab11-FIP2(S227A) did not affect localization with recycling system components or the normal function of apical recycling and transcytosis pathways. These results indicate that phosphorylation of Rab11-FIP2 on serine 227 by MARK2 regulates an alternative pathway modulating the establishment of epithelial polarity.

Pubmed ID: 16775013 RIS Download

Mesh terms: Adherens Junctions | Amino Acid Sequence | Animals | Calcium Signaling | Cell Polarity | Cells, Cultured | Dogs | Epithelial Cells | Gene Expression | Molecular Sequence Data | Mutation | Myosin Type V | Phosphorylation | Protein Binding | Protein Transport | Protein-Serine-Threonine Kinases | Rabbits | Receptor, PAR-1 | rab GTP-Binding Proteins

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Associated grants

  • Agency: NCI NIH HHS, Id: CA-68485
  • Agency: NIDDK NIH HHS, Id: DK-20593
  • Agency: NIDDK NIH HHS, Id: DK-43405
  • Agency: NIDDK NIH HHS, Id: DK-48370
  • Agency: NIDDK NIH HHS, Id: DK-58404
  • Agency: NICHD NIH HHS, Id: HD15052
  • Agency: NIDDK NIH HHS, Id: R01 DK-51970

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