Effects of mutation on regulation of the cellular src protein
- Author
- Reddy, Sita
- Physical Description
- 199 pages
- Additional Creators
- Pennsylvania State University
Access Online
- Summary
- The viral src (v-src) gene differs from the cellular src (c-src) gene by having scattered point mutations in the body of the gene and by an altered carboxyl terminus. The relative significance of these mutations for activating src transforming activity has been disputed since apparently conflicting results have been obtained by different laboratories in experiments using vectors encoding chimeric v(amino)/c(carboxyl)-src (v/c-src) constructs.
The uncontrolled factors in these early experiments which might account for the observed differences include (1) the expression levels of the src proteins; (2) the strain of v-src used; (3) the extent of c-src downstream flanking sequence (dsfs) included in the vectors; and (4) the cell types in which these v/c-src chimeras were tested.
The purpose of this thesis was (1) to unequivocally determine the significance of the c-src carboxyl terminus in src mediated transformation; (2) to determine the role of expression levels in v/c-src protein transforming activity; (3) to determine if viral strain differences affect the transforming potential of v/c-src constructs; and (4) to determine the significance of the c-src dsfs in src mediated transformation.
The primary findings are the following: The presence of the c-src carboxyl terminus represses complete transformation of NIH 3T3 cells. Differences in transforming potential of src proteins are evident only when a correct range of expression levels is used. (I show how dose-response is adequately modeled in terms of threshold levels). v-src strain specific mutations can strongly affect the transforming potential of v/c-src chimeric genes. The sequence of Schmidt-Ruppin D (SRD) strain v-src is presented. I show that the presence of a Val 461 $\to$ Met mutation in SRD v-src suppresses in vitro kinase activity. The presence of the c-src dsfs decreases src transforming activity. I conclude that pp60$\sp{\rm c-{\it src\/}}$ is primarily regulated by its carboxyl region and secondarily by other factors. - Other Subject(s)
- Dissertation Note
- Ph.D. The Pennsylvania State University 1988.
- Note
- Source: Dissertation Abstracts International, Volume: 50-05, Section: B, page: 1787.
Adviser: David Shalloway. - Part Of
- Dissertation Abstracts International
50-05B
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