MAP kinase-dependent pathways in cell cycle control

Abstract

Mitogen-activated protein kinases such as Erk1 and Erk2 serve as a paradigm for a growing family of proline-directed protein kinases that mediate entry, progression and exit from the cell cycle in diverse eukaryotic cells. These enzymes function within highly conserved modules of sequentially activating protein kinases that transduce signals from diverse extracellular stimuli. In vertebrates, at least three distinct kinases modules have been characterized. Mitogens induce the sequential activation of the kinases Raf1→Mek1→Erk2→Rsk via the G-protein Ras. Stress factors stimulate c-Jun activation through a related kinase pathway involving Mekk→Sek→SAPK c-Jun, and hsp27 phosphorylation via the MKK3→Hog→MAPKAPK-2 hsp27 route. Genetic and biochemical studies, for example from budding yeast, imply the existence of several related protein kinase modules that can operate in parallel or within integrated systems.