RGD Reference Report - A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor. - Rat Genome Database

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A kinase cascade leading to Rab11-FIP5 controls transcytosis of the polymeric immunoglobulin receptor.

Authors: Su, T  Bryant, DM  Luton, F  Verges, M  Ulrich, SM  Hansen, KC  Datta, A  Eastburn, DJ  Burlingame, AL  Shokat, KM  Mostov, KE 
Citation: Su T, etal., Nat Cell Biol. 2010 Dec;12(12):1143-53. Epub 2010 Oct 31.
RGD ID: 5131516
Pubmed: PMID:21037565   (View Abstract at PubMed)
PMCID: PMC3072784   (View Article at PubMed Central)
DOI: DOI:10.1038/ncb2118   (Journal Full-text)

Polymeric immunoglobulin A (pIgA) transcytosis, mediated by the polymeric immunoglobulin receptor (pIgR), is a central component of mucosal immunity and a model for regulation of polarized epithelial membrane traffic. Binding of pIgA to pIgR stimulates transcytosis in a process requiring Yes, a Src family tyrosine kinase (SFK). We show that Yes directly phosphorylates EGF receptor (EGFR) on liver endosomes. Injection of pIgA into rats induced EGFR phosphorylation. Similarly, in MDCK cells, pIgA treatment significantly increased phosphorylation of EGFR on various sites, subsequently activating extracellular signal-regulated protein kinase (ERK). Furthermore, we find that the Rab11 effector Rab11-FIP5 is a substrate of ERK. Knocking down Yes or Rab11-FIP5, or inhibition of the Yes-EGFR-ERK cascade, decreased pIgA-pIgR transcytosis. Finally, we demonstrate that Rab11-FIP5 phosphorylation by ERK controls Rab11a endosome distribution and pIgA-pIgR transcytosis. Our results reveal a novel Yes-EGFR-ERK-FIP5 signalling network for regulation of pIgA-pIgR transcytosis.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Pigr  (polymeric immunoglobulin receptor)
Yes1  (YES proto-oncogene 1, Src family tyrosine kinase)


Additional Information