Adhesion to the extracellular matrix via integrins triggers cell spreading, and extension of filopodia and lamellipodia. A driving force for the extension of filopodia and lamellipodia is the polymerization of actin. Act- in polymerization can be initiated by either of two mechanisms: by de novo polymerization, or the uncapping of capped actin filaments to expose the """"""""barbed"""""""" end of the filaments, onto which additional actin subunits can polymerize. Current evidence indicates that the Arp2/3 complex plays a critical role in nucleating de novo polymerization, and that the Arp2/3 complex is involved in the actin polymerization that occurs during extension of lamellipodia and filopodia. Since integrin engagement promotes the formation of filopodia and lamellipodia, it seems likely therefore that there is a link between integrins and the Arp2/3 complex. The focus of this proposal is to determine if such a link exists and the nature of it. I would like to determine if Arp2/3 function contributes to the integrin- mediated cytoskeletal events, whether the Arp2/3 complex is recruited to the integrins, and if the Arp2/3 complex is tyrosine phosphorylated in response to integrin engagement. My hypothesis is that association of the Arp2/3 complex with integrins and tyrosine phosphorylation is an important determinant of the ability of cells to undergo events that are essential for cell movement and tumor cell invasion. Hence, these studies will provide novel information regarding how cell adhesion and actin polymerization are coordinated to give rise to cell motility and will yield information that will allow for a better understanding of the genesis and progression of tumor cell invasion and metastasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM020610-01
Application #
6205425
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Flicker, Paula F
Project Start
2000-08-07
Project End
Budget Start
2000-08-07
Budget End
2001-08-06
Support Year
1
Fiscal Year
2000
Total Cost
$32,416
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599