Jimenez-Sanchez M, et al. (2007) Retrophosphorylation of Mkk1 and Mkk2 MAPKKs by the Slt2 MAPK in the Yeast Cell Integrity Pathway. J Biol Chem 282(43):31174-85
Abstract: In S. cerevisiae, a variety of stresses and aggressions to the cell wall stimulate the activation of the cell wall integrity (CWI) MAPK pathway, which triggers the expression of a series of genes important for the maintenance of cell wall homeostasis. This MAPK module lies downstream the Rho1 small GTPase and protein kinase C Pkc1, and consists of the MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the Slt2 MAPK. In agreement to previous reports suggesting that Mkk1 and Mkk2 were functionally redundant, we show here that both Mkk1 and Mkk2 alone or even chimerical proteins constructed by interchanging their catalytic and regulatory domains are able to efficiently maintain signal transduction through the pathway. Both Mkk1 and Mkk2 are phosphorylated in vivo concomitant to activation of the cell integrity pathway. Interestingly, hyperphosphorylation of the MEKs required not only the upstream components of the pathway, but also a catalytically competent Slt2 MAPK downstream. Active Slt2 purified from yeast extracts was able to phosphorylate Mkk1 and Mkk2 in vitro. We have mapped Ser50 as a direct phosphorylation target for Slt2 in Mkk2. However, substitution of all (S/T)-P canonical MAPK target sites to alanine did not totally abrogate Slt2-dependent Mkk2 phosphorylation. Mutation or deletion of a conserved MAPK-docking site at the N-terminal extension of Mkk2 precluded its interaction with Slt2 and negatively affected retrophosphorylation. Our data show that the CWI MAPKKs are targets for their downstream MAPK, suggesting the existence of complex feedback regulatory mechanisms at this level.
|Status: Published||Type: Journal Article||PubMed ID: 17711850|
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