Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway

Abstract

To cope with life‐threatening high osmolarity, yeast activates the high‐osmolarity glycerol (HOG) signaling pathway, whose core element is the Hog1 MAP kinase cascade. Activated Hog1 regulates the cell cycle, protein translation, and gene expression. Upstream of the HOG pathway are functionally redundant SLN1 and SHO1 signaling branches. However, neither the osmosensor nor the signal generator of the SHO1 branch has been clearly defined. Here, we show that the mucin‐like transmembrane proteins Hkr1 and Msb2 are the potential osmosensors for the SHO1 branch. Hyperactive forms of Hkr1 and Msb2 can activate the HOG pathway only in the presence of Sho1, whereas a hyperactive Sho1 mutant activates the HOG pathway in the absence of both Hkr1 and Msb2, indicating that Hkr1 and Msb2 are the most upstream elements known so far in the SHO1 branch. Hkr1 and Msb2 individually form a complex with Sho1, and, upon high external osmolarity stress, appear to induce Sho1 to generate an intracellular signal. Furthermore, Msb2, but not Hkr1, can also generate an intracellular signal in a Sho1‐independent manner.

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…Recently a second mucin-like protein, Hkr1, was shown to function together with Msb2 as an osmosensor in the S. cerevisiae Hog1 pathway (Tatebayashi et al, 2007). We detected single orthologues of Msb2, but not Hkr1, in all species studied except for S. pombe and R. oryzae.…”

Binding the Atypical RA Domain of Ste50p to the Unfolded Opy2p Cytoplasmic Tail Is Essential for the High-Osmolarity Glycerol Pathway

“…More recently, two membrane mucin-like molecules, Msb2p and Hkr1p, have been implicated as osmosensors that also function in the SHO1 branch of the HOG pathway (Tatebayashi et al, 2007). Genetically, Opy2p functions at or above the level of Ste50p/Ste11p at or downstream of Sho1p (Wu et al, 2006) and downstream of Msb2p and Hkr1p (Tatebayashi et al, 2007).…”

In vivo measurement of signaling cascade dynamics

“…Two input branches, the SLN1, 16,17 and SHO1 [18][19][20] branch, converge on the core MAP kinase kinase Pbs2. These two branches are redundant for cell survival under conditions of moderate osmotic stress.…”