Date of Graduation

2004

Document Type

Dissertation/Thesis

Abstract

Src family kinases play an essential role in many cellular processes, including tumor formation and metastasis. One mechanism of how this occurs in through the ability of Src to promote cell invasion by directly affecting actin filament integrity. Src activation results in a loss of bundled stress fibers and the formation of actin-rich podosomes that promote the invasive phenotype through extracellular matrix degradation. AFAP-110 is an adaptor molecule that interacts with the actin cytoskeleton and Src, as well as PKCα. In response to PKC phosphorylation, AFAP-110 is able to direct cSrc activation through SH3-mediated interactions, and promote the formation of podosomes and other motility structures. Chapter 1 of this dissertation is a literature review of Src, AFAP-110, and PKCα. Chapter 2 discusses the ability of AFAP-110 to direct cSrc activation and podosome formation in response to PKCα activation. Chapter 3 examines the ability of AFAP-110 to colocalize with inactive cSrc on perinuclear vesicles following stimulation and their transit to the ventral surface of the cell, as well as the construction of a temperature-sensitive mutant of vSrc that is tagged at the carboxy-terminal end. Chapter 4 examines the role of caspase 2 in the formation and maintenance of actin stress fibers.

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