Cdc42p-interacting protein Bem4p regulates the filamentous-growth mitogen-activated protein kinase pathway.
The ubiquitous Rho (Ras homology) GTPase Cdc42p can function in different settings to regulate cell polarity and cellular signaling. How Cdc42p and other proteins are directed to function in a particular context remains unclear. We show that the Cdc42p-interacting protein Bem4p regulates the mitogen-activated protein kinase (MAPK) pathway that controls filamentous growth in Saccharomyces cerevisiae. Bem4p controlled the filamentous-growth pathway but not other MAPK pathways (mating or high-osmolarity glycerol response [HOG]) that also require Cdc42p and other shared components. Bem4p associated with the plasma membrane (PM) protein, Sho1p, to regulate MAPK activity and cell polarization under nutrient-limiting conditions that favor filamentous growth. Bem4p also interacted with the major activator of Cdc42p, the guanine nucleotide exchange factor (GEF) Cdc24p, which we show also regulates the filamentous-growth pathway. Bem4p interacted with the pleckstrin homology (PH) domain of Cdc24p, which functions in an autoinhibitory capacity, and was required, along with other pathway regulators, to maintain Cdc24p at polarized sites during filamentous growth. Bem4p also interacted with the MAPK kinase kinase (MAPKKK) Ste11p. Thus, Bem4p is a new regulator of the filamentous-growth MAPK pathway and binds to general proteins, like Cdc42p and Ste11p, to promote a pathway-specific response.
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Andrew
A
Pitoniak
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Colin A
CA
Chavel
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Jacky
J
Chow
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Jeremy
J
Smith
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Diawoye
D
Camara
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Sheelarani
S
Karunanithi
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA.
Boyang
B
Li
Conway Institute, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Kennith H
KH
Wolfe
Department of Biological Sciences, SUNY-Buffalo, Buffalo, New York, USA pjcullen@buffalo.edu.
Paul J
PJ
Cullen
D000818:Animals; D016764:Cell Polarity / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000378:metabolism*
C100926:BEM4 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae