THE RAF-1 SERINE THREONINE PROTEIN-KINASE

Raf-1 belongs to a family of serine/threonine protein kinases which ar e highly conserved through evolution in multicellular organisms. Raf-1 kinase has gained much attention due to its function as a critical sh uttle enzyme that connects stimulation of growth factor receptors and protein kinase C at the cell membrane to changes in the expression of genes involved in the control of cell growth, differentiation and surv ival. Regulation of Raf-1 activity is complex and involves Ras, as wel l as several serine/threonine and tyrosine kinases. Through a series o f phosphorylation events, extracellular signals are connected through the Raf-1/MAP kinase pathway to activity-regulation of several oncogen e-class transcription factors via phosphorylation of specific serine r esidues. Under ordinary circumstances, the cascade involving Raf-1 eve ntually leads to changes in gene expression and protein synthesis. Upo n constitutive activation of Raf-1 kinase, as a result of genetic chan ges, a variety of cell types acquire a transformed phenotype.