Signaling Mucins and Scaffolds: Maintaining Specificity Between Related MAP Kinase Pathways
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A central question in the area of signal transduction is why pathways utilize common components. In budding yeast, three MAPK pathways (mating, HOG, and filamentous growth) use overlapping components yet induce specific responses. To better understand the regulation of the FG pathway, we examined FG in one of yeast’s native environments, the grape-producing plant Vitis vinifera. In this setting, different aspects of FG were induced in a temporal manner coupled to the nutrient cycle, which uncovered a multimodal feature of FG pathway signaling. FG pathway activity was modulated by the HOG pathway, which led to the finding that the signaling mucins Msb2p and Hkr1p, which operate at the head of the HOG pathway, differentially regulate the FG pathway. The two mucins exhibited different expression and secretion patterns, and their overproduction induced non-overlapping sets of target genes. Moreover, Msb2p had a function in cell polarization through the adaptor protein Sho1p that Hkr1p did not. Differential MAPK activation by signaling mucins brings to light a new point of discrimination between MAPK pathways. Pathway-specific regulators, such as scaffolds that insulate MAPK signaling, have been identified for the mating (Ste5p) and HOG (Pbs2p) pathways, but few pathway-specific regulators of the filamentous growth pathway have been characterized. We identified BEM4 in a genetic screen as a potential regulator of the filamentous growth pathway. Bem4p associated with multiple components of the pathway, including the polarity control Rho-like GTPase Cdc42p, the GEF Cdc24p, and the MAPKKK Ste11p. Bem4p also functioned in a protein complex with a cell-surface regulator of the filamentous growth pathway, Sho1p, and contributed to the surface localization of Cdc42p and effector PAK Ste20p. Bem4p did not play a major role in the mating or HOG pathways. Taken together, our findings identify a new regulator of the filamentous growth pathway that may participate in inducing a pathway-specific output.