Phosphorylation of GMF by c-Abl coordinates lamellipodial and focal adhesion dynamics

During cell migration a critical interdependence between protrusion and focal adhesion dynamics is established and tightly regulated through signaling cascades. Here we demonstrate that c-Abl, a non-receptor tyrosine kinase, can control these migratory structures through the regulation of two actin-...

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Bibliographic Details
Published inbioRxiv
Main Authors Gerlach, Brennan D, Liao, Guoning, Tubbesing, Kate, Rezey, Alyssa C, Wang, Ruping, Barroso, Margarida, Tang, Dale D
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 16.01.2018
Subjects
Actin
Cell adhesion & migration
Cell migration
Glia maturation factor
Kinases
N-WASP protein
Neuronal-glial interactions
Phosphorylation
Protein-tyrosine kinase receptors
Signal transduction
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Summary:During cell migration a critical interdependence between protrusion and focal adhesion dynamics is established and tightly regulated through signaling cascades. Here we demonstrate that c-Abl, a non-receptor tyrosine kinase, can control these migratory structures through the regulation of two actin-associated proteins, glia maturation factor- (GMF ) and Neural Wiskott-Aldrich syndrome protein (N-WASP). Phosphorylation of GMF at tyrosine-104 by c-Abl directs activated N-WASP (pY256) to the leading edge, where it can promote protrusion extension. Non-phosphorylated GMF guides N-WASP (pY256) to maturing focal adhesions to enhance further growth. Antagonizing this signaling pathway through knockdown or mutation of tyrosine-104 to its non-phosphorylated form attenuates migration, whereas the phospho-mimic mutant GMF enhances migration, thus demonstrating c-Abl, GMF , and activated N-WASP (pY256) as a critical signaling cascade for regulating migration in a primary human cell line.
DOI:10.1101/248914