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M J Welham

Publications and source records attributed to M J Welham.

20 records · Page 2Linked to original sources
PubMed1990

Mitogenesis induced by pp60v-src is not accompanied by increased expression of immediate early response genes.

Rat-1 cells infected with a temperature sensitive mutant of RSV (ts LA 29 Rat-1) can be rendered quiescent by serum deprivation at restrictive temperature. Shift to permissive conditions activates the v-src protein tyrosine kinase within 10 minutes and either this stimulus, or serum addition at restrictive temperature, leads to progression of the cell from G0 to G1, S-phase and mitosis. The effects of serum and temperature shift are not synergistic, suggesting that they may operate by convergent mechanisms. However, the characteristic serum-stimulated transient increases in transcripts of three immediate early response genes, c-fos, c-jun and c-myc are absent or much reduced when mitogenesis in ts LA 29 Rat-1 is induced by pp60v-src. Nonetheless, upon activating the pp60v-src protein kinase there is a marked and rapid increase in the ability of ts LA 29 Rat-1 nuclear extracts to retard the gel migration of oligonucleotides containing the AP-1 binding site, indicating that pp60v-src activity leads to an enhanced functioning of Fos and Jun related proteins that may, in turn, affect their transcriptional activation. Furthermore, these findings, and comparison with those of other laboratories, suggest that the mitogenic and transforming activities of pp60v-src have different effects on the transcription of immediate early response genes.

Animals↗
PubMed1988

A single point mutation has pleiotropic effects on pp60v-src function.

The Rous sarcoma virus mutant tsLA29 encodes a pp60v-src molecule that is temperature sensitive for both tyrosine kinase activity and its ability to locate at the cell periphery. The defect in localization appears to be due to a perturbation in events following complex dissociation, since the mutant enzyme shows a rapidly reversible association with the cytoskeleton when shifted between permissive and restrictive temperatures. Although tsLA29 pp60v-src differs from the wild type at three amino acid residues, studies with chimeric proteins show that only one of the mutations, an alanine-for-proline substitution at residue 507, accounts for all the temperature-sensitive characteristics. Moreover, a single second site mutation, at residue 427, can restore the wild phenotype. Cells infected with a chimeric virus encoding only the alanine substitution at position 507 have a conspicuously fusiform morphology, suggesting that this mutation also has subtle effects on pp60v-src function that are apparently compensated for by the other mutations in native tsLA29.

Animals↗