RRC ID 77424
Author Ideo H, Hoshi I, Yamashita K, Sakamoto M.
Title Phosphorylation and externalization of galectin-4 is controlled by Src family kinases.
Journal Glycobiology
Abstract Galectin-4 is a cytosolic protein that lacks a signal sequence but is externalized and binds to 3-O-sulfated glycoconjugates extracellularly. The mechanism of subcellular localization and externalization of galectin-4 has not yet been determined. A preliminary experiment using pervanadate (PV) showed that galectin-4 is tyrosine-phosphorylated in cells and suggested that Src kinases are involved. Cell transfection with galectin-4 and active Src plasmids showed that galectin-4 can be tyrosine phosphorylated by members of the Src kinase family. The C-terminal peptide YVQI of galectin-4 was found to play an important role in its tyrosine phosphorylation, and the SH2 domains of Src and SHP2 were found to bind to this peptide. Immunofluorescence analysis showed that galectin-4 and phosphorylated proteins were intensely stained in the area of membrane protrusions of PV-treated or Src-activated cells. Furthermore, MUC1 derived from NUGC-4 cells was observed to bind to galectin-4, and externalization of the bound molecules from the cell to the medium increased in the hyperphosphorylated condition. Study of the transfection of the mutant galectin-4 which lacks the C-terminal peptide revealed that the phosphorylation status is important for externalization of galectin-4. These results suggest that externalization of galectin-4 can be regulated by signaling molecules and that it may function intracellularly as an adaptor protein serving to modulate the trafficking of glycoproteins.
Volume 23(12)
Pages 1452-62
Published 2013-12-1
DOI 10.1093/glycob/cwt073
PII cwt073
PMID 24013903
MeSH Animals CHO Cells Cell Line, Tumor Cricetulus Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Galectin 4 / analysis Galectin 4 / chemistry* Galectin 4 / metabolism* Humans Phosphorylation Tyrosine / chemistry Tyrosine / metabolism src-Family Kinases / metabolism*
IF 4.06
Human and Animal Cells CHO-K1(RCB0285)