Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human

• Published in: Physiological reviews 1999-01, Vol.79 (1), p.143-180
• Main Authors: WIDMANN, CHRISTIAN, GIBSON, SPENCER, JARPE, MATTHEW B, JOHNSON, GARY L
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Animals; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Drug therapy; Evolution, Molecular; Fungal Proteins - genetics; Fungal Proteins - metabolism; Humans; MAP Kinase Kinase Kinases; Mitogen-Activated Protein Kinase Kinases; Protein Kinases - genetics; Protein Kinases - metabolism; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics
• ISSN: 0031-9333; 1522-1210
• DOI: 10.1152/physrev.1999.79.1.143

CHRISTIAN WIDMANN , SPENCER GIBSON , MATTHEW B. JARPE , AND GARY L. JOHNSON Program in Molecular Signal Transduction, Division of Basic Sciences, National Jewish Medical and Research Center, Denver, Colorado Widmann, Christian, Spencer Gibson, Matthew B. Jarpe, and Gary L. Johnson. Mitogen-Activated Protein Kinase: Conservation of a Three-Kinase Module From Yeast to Human. Physiol. Rev . 79: 143-180, 1999.   Mitogen-activated protein kinases (MAPK) are serine-threonine protein kinases that are activated by diverse stimuli ranging from cytokines, growth factors, neurotransmitters, hormones, cellular stress, and cell adherence. Mitogen-activated protein kinases are expressed in all eukaryotic cells. The basic assembly of MAPK pathways is a three-component module conserved from yeast to humans. The MAPK module includes three kinases that establish a sequential activation pathway comprising a MAPK kinase kinase (MKKK), MAPK kinase (MKK), and MAPK. Currently, there have been 14 MKKK, 7 MKK, and 12 MAPK identified in mammalian cells. The mammalian MAPK can be subdivided into five families: MAPK erk1/2 , MAPK p38 , MAPK jnk , MAPK erk3/4 , and MAPK erk5 . Each MAPK family has distinct biological functions. In Saccharomyces cerevisiae , there are five MAPK pathways involved in mating, cell wall remodelling, nutrient deprivation, and responses to stress stimuli such as osmolarity changes. Component members of the yeast pathways have conserved counterparts in mammalian cells. The number of different MKKK in MAPK modules allows for the diversity of inputs capable of activating MAPK pathways. In this review, we define all known MAPK module kinases from yeast to humans, what is known about their regulation, defined MAPK substrates, and the function of MAPK in cell physiology.