Stress-specific Activation Mechanisms for the “Cell Integrity” MAPK Pathway

• Published in: The Journal of biological chemistry Vol. 279; no. 4; p. 2616
• Main Authors: Jacob C. Harrison, Trevin R. Zyla, Elaine S. G. Bardes, Daniel J. Lew
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 23-01-2004
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M306110200

Many environmental stresses trigger cellular responses by activating mitogen-activated protein kinase (MAPK) pathways. Once
activated, these highly conserved protein kinase cascades can elicit cellular responses such as transcriptional activation
of response genes, cytoskeletal rearrangement, and cell cycle arrest. The mechanism of pathway activation by environmental
stresses is in most cases unknown. We have analyzed the activation of the budding yeast “cell integrity” MAPK pathway by heat
shock, hypoosmotic shock, and actin perturbation, and we report that different stresses regulate this pathway at different
steps. In no case can MAPK activation be explained by the prevailing view that stresses simply induce GTP loading of the Rho1p
GTPase at the “top” of the pathway. Instead, our findings suggest that the stresses can modulate at least three distinct kinases
acting between Rho1p and the MAPK. These findings suggest that stresses provide “lateral” inputs into this regulatory pathway,
rather than operating in a linear “top-down” manner.