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Sci. Signal., 25 February 2014
Vol. 7, Issue 314, p. ra21
[DOI: 10.1126/scisignal.2004780]

RESEARCH ARTICLES

Yeast Osmosensors Hkr1 and Msb2 Activate the Hog1 MAPK Cascade by Different Mechanisms

Keiichiro Tanaka1*, Kazuo Tatebayashi1,2{dagger}, Akiko Nishimura1,2, Katsuyoshi Yamamoto1, Hui-Yu Yang1, and Haruo Saito1,2{dagger}

1 Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
2 Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.

* Present address: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT 06511, USA.

Abstract: To cope with environmental high osmolarity, the budding yeast Saccharomyces cerevisiae activates the mitogen-activated protein kinase (MAPK) Hog1, which controls an array of osmoadaptive responses. Two independent, but functionally redundant, osmosensing systems involving the transmembrane sensor histidine kinase Sln1 or the tetraspanning membrane protein Sho1 stimulate the Hog1 MAPK cascade. Furthermore, the Sho1 signaling branch itself also involves the two functionally redundant osmosensors Hkr1 and Msb2. However, any single osmosensor (Sln1, Hkr1, or Msb2) is sufficient for osmoadaptation. We found that the signaling mechanism by which Hkr1 or Msb2 stimulated the Hog1 cascade was specific to each osmosensor. Specifically, activation of Hog1 by Msb2 required the scaffold protein Bem1 and the actin cytoskeleton. Bem1 bound to the cytoplasmic domain of Msb2 and thus recruited the kinases Ste20 and Cla4 to the membrane, where either of them can activate the kinase Ste11. The cytoplasmic domain of Hkr1 also contributed to the activation of Ste11 by Ste20, but through a mechanism that involved neither Bem1 nor the actin cytoskeleton. Furthermore, we found a PXXP motif in Ste20 that specifically bound to the Sho1 SH3 (Src homology 3) domain. This interaction between Ste20 and Sho1 contributed to the activation of Hog1 by Hkr1, but not by Msb2. These differences between Hkr1 and Msb2 may enable differential regulation of these two proteins and provide a mechanism through Msb2 to connect regulation of the cytoskeleton with the response to osmotic stress.

{dagger} Corresponding author. E-mail: tategone{at}ims.u-tokyo.ac.jp (K.T.); h-saito{at}ims.u-tokyo.ac.jp (H.S.)

Citation: K. Tanaka, K. Tatebayashi, A. Nishimura, K. Yamamoto, H.-Y. Yang, H. Saito, Yeast Osmosensors Hkr1 and Msb2 Activate the Hog1 MAPK Cascade by Different Mechanisms. Sci. Signal. 7, ra21 (2014).

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