Molecular recognitions in the MAP kinase cascades.
The mitogen-activated protein kinase (MAPK) cascades play a pivotal role in many aspects of cellular functions, and are evolutionarily conserved from yeast to mammals. In mammals, there are four subfamily members in the MAPKs. Each MAPK has its own activators, substrates and inactivators. In order to achieve normal cellular functions, the MAPK cascades should transduce signals with high efficiency and fidelity. However, the molecular basis for the mechanism underlying the specific reactions in the MAPK cascades has not been fully understood. The MAPKs form a globular structure without a distinct domain specific for protein-protein interactions. Recent studies revealed two mechanisms regulating the signalling, the docking interaction and the scaffolding. The docking interaction is achieved through the common docking domain (the CD domain) on MAPKs, and is different from a transient enzyme-substrate interaction through the active centre of the enzymes. Almost all the MAPK-interacting molecules have a conserved motif interacting with the CD domain. The scaffolding usually utilizes a third molecule to tether several components of the MAPK cascades. Both of them are thought to regulate the enzymatic specificity and efficiency.
Tanoue
Takuji
T
Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Sakyo, Kyoto 606-8502, Japan.
Nishida
Eisuke
E
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D029721:Drosophila Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D029721:Drosophila Proteins; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C086795:rl protein, Drosophila; D010749:Phosphoprotein Phosphatases