EGF receptor signaling stimulates SRC kinase phosphorylation of clathrin, influencing clathrin redistribution and EGF uptake

Andrew Wilde, Eric C. Beattie, Lawrence Lem, David A. Riethof, Shu Hui Liu, William C. Mobley, Philippe Soriano, Frances M. Brodsky

Research output: Contribution to journalArticlepeer-review

289 Scopus citations

Abstract

Epidermal growth factor (EGF) binding to its receptor causes rapid phosphorylation of the clathrin heavy chain at tyrosine 1477, which lies in a domain controlling clathrin assembly. EGF-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of SRC kinase by EGF receptor (EGFR) signaling. In cells lacking SRC kinase, or cells treated with a specific SRC family kinase inhibitor, EGF stimulation of clathrin phosphorylation and redistribution does not occur, and EGF endocytosis is delayed. These observations demonstrate a role for SRC kinase in modification and recruitment of clathrin during ligand-induced EGFR endocytosis and thereby define a novel effector mechanism for regulation of endocytosis by receptor signaling.

Original languageEnglish
Pages (from-to)677-687
Number of pages11
JournalCell
Volume96
Issue number5
DOIs
StatePublished - 5 Mar 1999
Externally publishedYes

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