FIGURE 10:

Model for Cbk1 and Bck2 function with regard to CWI pathway signaling. There are two distinct roles for Cbk1 and Bck2 in CWI-pathway signaling: 1) Cbk1 promotes Mpk1 activation via Bck2 during stress-dependent CWI activation. Cbk1 and Bck2 function after MAPKK-dependent Mpk1 phosphorylation, similar to Knr4 and the chaperone Hsp90. 2) Cbk1, Bck2, and the MAPK phosphatase Sdp1 cooperatively function to inactivate Mpk1 during heat shock adaptation. During heat shock, but not other CWI-activating stresses, Bck2 and Sdp1 localize to mitochondria and other cytoplasmic puncta, where they are sequestered from Mpk1. During heat shock adaptation, Cbk1 mediates the release of Bck2 and Sdp1 phosphatase from mitochondria/cytoplasmic puncta, leading to Mpk1 dephosphorylation and inactivation.