Accession Number:

ADA415773

Title:

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

Descriptive Note:

Annual summary rept. 1 Mar 2002-28 Feb 2003

Corporate Author:

WISCONSIN UNIV-MADISON

Report Date:

2003-03-01

Pagination or Media Count:

9.0

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE