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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.

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


  • Ducharme NA
  • Hales CM
  • Lapierre LA
  • Ham AJ
  • Oztan A
  • Apodaca G
  • Goldenring JR


Molecular biology of the cell

Publication Data

August 28, 2006

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

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