HGF-induced migration depends on the PI(3,4,5)P₃-binding microexon-spliced variant of the Arf6 exchange factor cytohesin-1.

ABSTRACT: Differential inclusion or skipping of microexons is an increasingly recognized class of alternative splicing events. However, the functional significance of microexons and their contribution to signaling diversity is poorly understood. The Met receptor tyrosine kinase (RTK) modulates invasive growth and migration in development and cancer. Here, we show that microexon switching in the Arf6 guanine nucleotide exchange factor cytohesin-1 controls Met-dependent cell migration. Cytohesin-1 isoforms, differing by the inclusion of an evolutionarily conserved three-nucleotide microexon in the pleckstrin homology domain, display differential affinity for PI(4,5)P₂ (triglycine) and PI(3,4,5)P₃ (diglycine). We show that selective phosphoinositide recognition by cytohesin-1 isof

SUBMITTER: Ratcliffe CDH 

PROVIDER: S-EPMC6314551 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature