EGF Receptor Signaling Stimulates SRC Kinase Phosphorylation of Clathrin, Influencing Clathrin Redistribution and EGF Uptake

Cell. 1999 Mar 5;96(5):677-87. doi: 10.1016/s0092-8674(00)80578-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Transport
  • Cattle
  • Clathrin / metabolism*
  • Endocytosis / drug effects*
  • Epidermal Growth Factor / metabolism*
  • ErbB Receptors / physiology*
  • Humans
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism*

Substances

  • Clathrin
  • Ligands
  • Recombinant Fusion Proteins
  • Epidermal Growth Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases