title: The lethality of p60v-src in Saccharomyces cerevisiae and the activation of p34CDC28 kinase are dependent on the integrity of the SH2 domain.
abstract: The lethal effects of the expression of the oncogenic protein tyrosine kinase p60v-src in Saccharomyces cerevisiae are associated with a loss of cell cycle control at the G1/S and G2/M checkpoints. Results described here indicate that the ability of v-Src to kill yeast is dependent on the integrity of the SH2 domain, a region of the Src protein involved in recognition of proteins phosphorylated on tyrosine. Catalytically active v-Src proteins with deletions in the SH2 domain have little effect on yeast growth, unlike wild-type v-Src protein, which causes accumulation of large-budded cells, perturbation of spindle microtubules and increased DNA content when expressed. The proteins phosphorylated on tyrosine in cells expressing v-Src differ from those in cells expressing a Src protein with a deletion in the SH2 domain. Also, unlike the wild-type v-Src protein, which drastically increases histone H1-associated Cdc28 kinase activity, c-Src and an altered v-Src protein have no effect on Cdc28 kinase activity. These results indicate that the SH2 domain is functionally important in the disruption of the yeast cell cycle by v-Src.
authors.affiliation: Department of Biochemistry, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: F
authors.initials: F
authors.lastname: Boschelli
authors.forename: S M
authors.initials: SM
authors.lastname: Uptain
authors.forename: J J
authors.initials: JJ
authors.lastname: Lightbody
mesh_terms: D017489:CDC28 Protein Kinase, S cerevisiae / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005656:Fungal Proteins / Q000032:analysis; D015966:Gene Expression Regulation, Fungal; D015688:Oncogene Protein pp60(v-src) / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D010641:Phenotype; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D019000:Phosphotyrosine; D006656:Protamine Kinase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D017384:Sequence Deletion; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D005656:Fungal Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D006656:Protamine Kinase; D017489:CDC28 Protein Kinase, S cerevisiae