Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade.
Production of the essential phospholipid PI4P at the Golgi by the Pik1 kinase is required for protein secretion, while a distinct pool of PI4P generated by the Stt4 kinase is critical for normal actin cytoskeleton organization. We identify a transmembrane protein that stabilizes Stt4 at the plasma membrane where it directs synthesis of PI4P, which is required for activation of the Rho1/Pkc1-mediated MAP kinase cascade. Inactivation of Stt4 or the PI4P 5-kinase Mss4 results in mislocalization of the Rho-GTPase GEF Rom2. Rom2 binds PI4,5P(2) through its PH domain and represents the first identified effector in the Stt4-Mss4 pathway. Based on these results, we propose that Stt4-Mss4 generates PI4,5P(2) at the plasma membrane, required to recruit/activate effector proteins such as Rom2.
Audhya
Anjon
A
Division of Cellular and Molecular Medicine, The Howard Hughes Medical Institute, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Emr
Scott D
SD
D019870:1-Phosphatidylinositol 4-Kinase / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism*; D005800:Genes, Fungal; D016153:Genes, Suppressor; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); D011493:Protein Kinase C; D011506:Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D005656:Fungal Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C037178:phosphatidylinositol 4-phosphate; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C097993:Pkc1 protein, Trichoderma reesei; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; C112465:STT4 protein, S cerevisiae; C489795:MSS4 protein, S cerevisiae; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases