| Title: | A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission |
| Author(s): | Bardwell AJ; Flatauer LJ; Matsukuma K; Thorner J; Bardwell L; |
| Address: | "Department of Developmental and Cell Biology, University of California, Irvine, California 92697, USA. bardwell@uci.edu" |
| ISSN/ISBN: | 0021-9258 (Print) 1083-351X (Electronic) 0021-9258 (Linking) |
| Abstract: | "The recognition of mitogen-activated protein kinases (MAPKs) by their upstream activators, MAPK/ERK kinases (MEKs), is crucial for the effective and accurate transmission of many signals. We demonstrated previously that the yeast MAPKs Kss1 and Fus3 bind with high affinity to the N terminus of the MEK Ste7, and proposed that a conserved motif in Ste7, the MAPK-docking site, mediates this interaction. Here we show that the corresponding sequences in human MEK1 and MEK2 are necessary and sufficient for the direct binding of the MAPKs ERK1 and ERK2. Mutations in MEK1, MEK2, or Ste7 that altered conserved residues in the docking site diminished binding of the cognate MAPKs. Furthermore, short peptides corresponding to the docking sites in these MEKs inhibited MEK1-mediated phosphorylation of ERK2 in vitro. In yeast cells, docking-defective alleles of Ste7 were modestly compromised in their ability to transmit the mating pheromone signal. This deficiency was dramatically enhanced when the ability of the Ste5 scaffold protein to associate with components of the MAPK cascade was also compromised. Thus, both the MEK-MAPK docking interaction and binding to the Ste5 scaffold make mutually reinforcing contributions to the efficiency of signaling by this MAPK cascade in vivo" |
| Keywords: | "*Adaptor Proteins, Signal Transducing Alleles Amino Acid Motifs Amino Acid Sequence Binding Sites *Carrier Proteins Conserved Sequence Dose-Response Relationship, Drug Fungal Proteins/metabolism Genes, Fungal Glutathione Transferase/metabolism *MAP Kinase;" |
| Notes: | "MedlineBardwell, A J Flatauer, L J Matsukuma, K Thorner, J Bardwell, L eng R01 GM021841/GM/NIGMS NIH HHS/ GM60366/GM/NIGMS NIH HHS/ GM21841/GM/NIGMS NIH HHS/ R01 GM060366/GM/NIGMS NIH HHS/ R01 GM060366-01/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2001/01/13 J Biol Chem. 2001 Mar 30; 276(13):10374-86. doi: 10.1074/jbc.M010271200. Epub 2000 Dec 28" |
