Conformational searches on three closely related pp60 c-src protein tyrosine kinase inhibitors of varying potencies were performed to determine a structural basis for their activity. The first was a linear peptide (PDNEYAFFQf), the second its 10-membered cyclic analogue, and the third a cyclic analo
Functions of the v-SRC protein tyrosine kinase
✍ Scribed by V. Fincham; M. Frame; B. Haefner; M. Unlu; A. Wyke; J. Wyke
- Publisher
- Elsevier Science
- Year
- 1994
- Tongue
- English
- Weight
- 375 KB
- Volume
- 18
- Category
- Article
- ISSN
- 1065-6995
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✦ Synopsis
ABSTRACT
The peripheral non‐receptor tyrosine kinase oncoprotein, v‐Src, has pleiotropic effects. It is a mitogen for quiescent cells, substituting for both competence and progression factor‐mediated signals but it also induces cellular morphological transformation. We are dissecting the activities of v‐Src by studying mutant proteins, including those with temperature sensitive (ts) effects, in different cellular backgrounds. Activation of a ts v‐Src kinase rapidly increases activity of both the transcription factor, AP‐1, and MAP kinase, an enzyme that enhances AP‐1 activity by both phosphorylation of c‐Jun and increased c‐fos transcription; the relative contribution of these two events depends on the cells in which v‐Src is expressed. Transient early AP‐1 activation requires proper location of v‐Src at the cell periphery and it is essential for mitogenesis. It is not, however, sufficient for entry into S‐phase, there being a second need for v‐Src later in G~1~. Transformation by v‐Src does not require AP‐1 activation but seems linked to events at the cell periphery, notably phosphorylation of proteins that bind to the v‐Src SH3 domain such as the p85 subunit of PI‐3 kinase.
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