Characterization of Ligand-Induced Endocytosis of EGF-Receptors

Abstract

Under the auspices of this training Fellowship (May 9, 1994-November 9, 1997) I have undertaken studies on the molecular mechanisms that govern ligand-induced endocytosis of epidermal growth factor receptors (EGFR) and the role of regulated endocytosis of EGFR in controlling EGFR signaling. To this end, I developed a novel cell-free assay which reconstitutes the ligand-induced and EGFR tyrosine kinase-dependent recruitment of EGFR into cathrine coated pits. I also showed that activation of small Rho-family GTPases, which occurs in response to growth factors, can negatively regulate receptor-mediated endocytosis. In following up this discovery I have provided new and direct evidence for the involvement of the actin cytoskeleton in early events in receptor-mediated endocytosis. Finally, I have begun to explore the role of an EGFR tyrosine kinase substrate, Eps15, in receptor-mediated endocytosis. Eps15 is the prototype member of a growing family of EH (Eps15-homology) domain-containing proteins required for intracellular membrane trafficking. This successful training period has resulted in five manuscripts published in first-rate journals and one manuscript currently under review. It has paved the way for my continuing career objectives in cancer and medical research.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 1997
Accession Number
ADA344945

Entities

People

  • Sandra L. Schmid

Organizations

  • Scripps Research

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Cell Membrane
  • Cell Physiological Processes
  • Cells
  • Cellular Structures
  • Chemical Synthesis
  • Chemistry
  • Cytoskeleton
  • Growth Factors
  • Health Services
  • Peptide Growth Factors
  • Proteins
  • Training
  • Tyrosine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Technical Research and Report Writing.