Identification of MAGI-3 as a transforming growth factor-alpha tail binding protein.

Franklin JL, Yoshiura K, Dempsey PJ, Bogatcheva G, Jeyakumar L, Meise KS, Pearsall RS, Threadgill D, Coffey RJ
Exp Cell Res. 2005 303 (2): 457-70

PMID: 15652357 · DOI:10.1016/j.yexcr.2004.10.007

The cytoplasmic domain of the transforming growth factor-alpha precursor (proTGFalpha) contains a C-terminal PSD-95/SAP90, Discs Large, and Zona Occludens-1 (PDZ) recognition motif (TVV). By yeast two-hybrid screening of a mouse embryo library, we have found that a third member of a family of PDZ-containing proteins, membrane associated guanylate kinase inverted-3 (MAGI-3), binds to TGFalpha's TVV. MAGI-3 is widely expressed in multiple mouse tissues, including brain. Immunolocalization showed that MAGI-3 and TGFalpha were colocalized in neurons in the cortex and dentate gyrus, as well as in ependymal cells and some astrocytes. In vitro, proTGFalpha bound the PDZ-1 domain of MAGI-3 and MAGI-2, but not MAGI-1. MAGI-3 and the 17-kDa cell surface form of proTGFalpha interact transiently in MDCK cells stably transfected with both MAGI-3 and human proTGFalpha cDNAs. MAGI-3 and wild-type proTGFalpha colocalize at the cell surface. In contrast, MAGI-3 forms a stable complex with membrane-fixed TGFalpha early in the secretory pathway and interacts with immature and cell surface forms of membrane-fixed TGFalpha. Overexpression of MAGI-3 resulted in increased levels of TGFalpha in the basolateral medium of polarized MDCK cells, suggesting that MAGI-3 has a role in efficient trafficking of TGFalpha to the cell surface in polarized epithelial cells.

MeSH Terms (24)

Adaptor Proteins, Signal Transducing Animals Base Sequence Binding Sites Brain Carrier Proteins Cell Line DNA, Complementary Dogs Epithelial Cells Guanylate Kinases Humans Immunohistochemistry Male Mice Mice, Inbred C57BL Nucleoside-Phosphate Kinase Protein Precursors Proteins Recombinant Fusion Proteins Signal Transduction Transfection Transforming Growth Factor alpha Two-Hybrid System Techniques

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