Raf-1 interferes with Ras and Rap1A effector functions in yeast

• Published in: Molecular biology of the cell Vol. 5; no. 2; pp. 173 - 181
• Main Authors: Ruggieri, R, Macdonald, S G, Callow, M, McCormick, F
• Format: Journal Article
• Language: English
• Published: United States 01-02-1994
• Subjects: Cell Cycle Proteins; Fungal Proteins - metabolism; Genes, ras; GTP-Binding Proteins - metabolism; Guanine Nucleotide Exchange Factors; Guanosine Triphosphate - metabolism; Humans; Phenotype; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-raf; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; rap GTP-Binding Proteins; ras-GRF1; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Signal Transduction; Temperature; Transcription Factors - metabolism
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.5.2.173

Raf-1 is a serine/threonine kinase that acts downstream of Ras in mitogenic signal transduction pathways, but the mechanism by which Ras transmits signals to Raf-1 is not known. We have examined the interaction between Raf-1 and human H-ras in three different systems that utilize H-ras-induced phenotypes in Saccharomyces cerevisiae. In each system, the effects of H-ras depend on guanosine triphosphate and appear to be mediated through the H-ras effector binding region. H-ras effector function was blocked in each case by expression of the N-terminal regulatory domain of Raf-1. These inhibitory effects did not require the Raf-1 kinase domain. Raf-1 also blocked Rap1A effector function in S. cerevisiae. Raf-1, therefore, appears to interact with H-Ras and Rap1A in these in vivo systems with properties that suggest it is an immediate downstream effector.