Journal article
PKD Controls αvβ3 Integrin Recycling and Tumor Cell Invasive Migration through Its Substrate Rabaptin-5
C Christoforides, E Rainero, KK Brown, JC Norman, A Toker
Developmental Cell | CELL PRESS | Published : 2012
Abstract
Integrin recycling is critical for cell migration. Protein kinase D (PKD) mediates signals from the platelet-derived growth factor receptor (PDGF-R) to control αvβ3 integrin recycling. We now show that Rabaptin-5, a Rab5 effector in endosomal membrane fusion, is a PKD substrate. PKD phosphorylates Rabaptin-5 at Ser407, and this is both necessary and sufficient for PDGF-dependent short-loop recycling of αvβ3, which in turn inhibits α5β1 integrin recycling. Rab4, but not Rab5, interacts with phosphorylated Rabaptin-5 toward the front of migrating cells to promote delivery of αvβ3 to the leading edge, thereby driving persistent cell motility and invasion that is dependent on this integrin. Cons..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Juan Bonifacino and Peter Storz for providing reagents and Lewis Cantley, Sheila Thomas, Jeffrey Settleman, Patricia Muller, Karen Vousden, and members of the Toker, Norman, and Wenyi Wei laboratories for advice and discussions. This study was supported in part by grants from the National Institutes of Health (CA075134 and CA096710 to A.T.), The Department of Defense Breast Cancer Research program (BC061404 to C.C.), Cancer Research UK (to J.C.N. and E.R.), and the Genesis Oncology Trust of New Zealand (GOT-1040-JGPDF to K.K.B.). E.R. is supported by a fellowship from the West of Scotland Women's Bowling Association.