Ack-1 Tyrosine Kinase Regulates Integrin Signaling Leading to Breast Cell Migration

Abstract

Appropriate interactions between breast cells and the ECM via alpha2beta 1 integrin help to establish normal cellular structure and differentiation. During transformation to a carcinoma, these normal interactions with the ECM are profoundly altered, resulting in cells that lose their specialization and lose control of their growth. Ultimately, these cells become invasive, and then migrate through the connective tissue environment to form distant metastases. We have previously found that Ack 1 tyrosine kinase enhances alpha2beta 1 integrin-induced cell migration and regulates signaling components downstream of the integrin. In the course of the research I have determined that Ack-1 is phosphorylated upon collagen stimulation and that this phosphorylation is dependent on Src and FAK kinases. Furthermore, I found that FAK is not required for Ack-l association with p130Cas or Src and that Src is not necessary for p130Cas and FAK association with Ack-1. I also determined that Ack-1 associates with the SH3 domains of p130Cas, Src and Spectrin, which suggest direct binding between these molecules.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2003
Accession Number
ADA415773

Entities

People

  • Katarzyna Modzelewska
  • Patricia J. Keely

Organizations

  • University of Wisconsin–Madison

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Abstracts
  • Antibodies
  • Biomedical Research
  • Cell Membrane Structures
  • Cell Movement
  • Cells
  • Cellular Structures
  • Chemical Compounds
  • Chemistry
  • Collagen
  • Connective Tissue
  • Inhibitors
  • Integrins
  • Kinases
  • Migration
  • Phosphorylation
  • Tyrosine

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Nanofabrication and Microfabrication.