Hawle P, et al. (2007) Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase C mitogen-activated protein kinase pathway functionality by interaction with Hog1p and Slt2p (Mpk1p). Eukaryot Cell 6(3):521-32
Abstract: The yeast S. cerevisiae utilizes rapidly responding mitogen activated protein kinase (MAPK) signaling cascades to adapt efficiently to a changing environment. Here we report, that phosphorylation of Cdc37p, an Hsp90 co-chaperone, by Caseine kinase 2 (CK2) controls the functionality of two MAP kinase cascades in yeast. These pathways, the high osmolarity glycerol (HOG) and the cell integrity (PKC) MAP kinase pathway, mediate adaptive responses to high osmotic and cell wall stress, respectively. Mutation of the phosphorylation site Ser14 in Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by Calcofluor White (CFW). We found that cellular levels of the MAP kinases Hog1p and Slt2p (Mpk1p) are reduced in a cdc37 S14A mutant and consequently downstream responses mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something which has not been reported previously. The interaction of Hsp90, Slt2p and Hog1p with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our biochemical data show, that the osmo-sensitive phenotype of cdc37-S14A is due to the loss of the interaction between Cdc37p, Hog1p and Hsp90. Likewise during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is crucial for Slt2p-dependent downstream responses, such as the activation of the transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAP kinase signaling.
|Status: Published||Type: Journal Article||PubMed ID: 17220467|
Topics addressed in this paper
Number of different genes curated to this paper: 7
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.