Abstract
dc:description.abstractThe cSrc oncogene directs the reorganization of the actin cytoskeleton in both normal and transformed cells. Mutation of protein binding domains (SH2 and SH3) from cSrc results in the deregulation of the kinase and the transformation of cells, while deletion of these domains blocks transformation by active forms of Src. This indicates that SH2/SH3 binding partners for cSrc may play a crucial role in the regulation of this kinase as well as the fulfillment of cSrc-directed functions. One SH2/SH3 binding partner for cSrc being investigated for its role in cSrc transformation is the a&barbelow;ctin f&barbelow;ilament-a&barbelow;ssociated p&barbelow;rotein, AFAP-110. AFAP-110 represents a potential regulator of the actin cytoskeleton, as it associated with actin structures and contains an intrinsic potential to direct the reorganization of the cytoskeleton in a manner which resembles Src transformation. In this work we addressed this potential for AFAP-110 to induce actin reorganization. Immunoblot and immunofluorescence analyses were used to investigate this potential. The results indicate that AFAP-110 binds actin directly and can induce cytoskeletal reorganizations in multiple cells types. Additionally, AFAP-110 can activate cSrc in an SH3 domain-dependent mechanism. This ability is revealed upon phosphorylation by PKC, which induces a conformational change in AFAP-110. Both SH3 interactions with cSrc and PH domain interactions with PKC are required for this result, as abrogation of either interaction blocks both the activation of cSrc and the reorganization by PKC. These results allow us to conclude that AFAP-110 can activate cSrc in response to cellular signals.
Degree
thesis:*- Name thesis:degree_name
- PhD
- Level thesis:degree_level
- Dissertation
- Discipline thesis:degree_discipline
- Microbiology, Immunology, and Cell Biology
- Year dc:date.available
- 2003
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Baisden, Joseph Myers
- Contributors dc:contributor
-
- Daniel C. Flynn.
- Thomas A. Elliott
- Stephaen G. Graber
- Bing-Hua Jiang
- Mary J. Wimmer
Subjects
dc:subject × 3Identifiers
dc:identifier.*- Identifier
- https://researchrepository.wvu.edu/etd/871
- OAI identifier oai:identifier
- oai:researchrepository.wvu.edu:etd-1874