A conserved docking motif in MAP kinases common to substrates, activators and regulators

• Published in: Nature cell biology Vol. 2; no. 2; pp. 110 - 116
• Main Authors: Nishida, Eisuke, Tanoue, Takuji, Adachi, Makoto, Moriguchi, Tetsuo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.02.2000
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Amino acids; Binding Sites; Binding sites (Biochemistry); Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cellular signal transduction; Conserved Sequence; Dual Specificity Phosphatase 6; Enzymes; Kinases; MAP Kinase Kinase 1; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - metabolism; Models, Molecular; Molecular Sequence Data; p38 Mitogen-Activated Protein Kinases; Phosphatase; Phosphorylation; Physiological aspects; Protein Binding; Protein kinases; Protein Tyrosine Phosphatases - metabolism; Protein-Serine-Threonine Kinases - metabolism; Proteins; Signal transduction; Transcription factors
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/35000065

Mitogen-activated protein kinases (MAPKs) are specifically phosphorylated and activated by the MAPK kinases, phosphorylate various targets such as MAPK-activated protein kinases and transcription factors, and are inactivated by specific phosphatases. Recently, docking interactions via the non-catalytic regions of MAPKs have been suggested to be important in regulating these reactions. Here we identify docking sites in MAPKs and in MAPK-interacting enzymes. A docking domain in extracellular-signal-regulated kinase (ERK), a MAPK, serves as a common site for binding to the MAPK kinase MEK1, the MAPK-activated protein kinase MNK1 and the MAPK phosphatase MKP3. Two aspartic acids in this domain are essential for docking, one of which is mutated in the sevenmaker mutant of Drosophila ERK/Rolled. A corresponding domain in the MAPKs p38 and JNK/SAPK also serves as a common docking site for their MEKs, MAPK-activated protein kinases and MKPs. These docking interactions increase the efficiency of the enzymatic reactions. These findings reveal a hitherto unidentified docking motif in MAPKs that is used in common for recognition of their activators, substrates and regulators.