title: Osmostress induces autophosphorylation of Hog1 via a C-terminal regulatory region that is conserved in p38α.
abstract: Many protein kinases require phosphorylation at their activation loop for induction of catalysis. Mitogen-activated protein kinases (MAPKs) are activated by a unique mode of phosphorylation, on neighboring Tyrosine and Threonine residues. Whereas many kinases obtain their activation via autophosphorylation, MAPKs are usually phosphorylated by specific, dedicated, MAPK kinases (MAP2Ks). Here we show however, that the yeast MAPK Hog1, known to be activated by the MAP2K Pbs2, is activated in pbs2Δ cells via an autophosphorylation activity that is induced by osmotic pressure. We mapped a novel domain at the Hog1 C-terminal region that inhibits this activity. Removal of this domain provides a Hog1 protein that is partially independent of MAP2K, namely, partially rescues osmostress sensitivity of pbs2Δ cells. We further mapped a short domain (7 amino acid residues long) that is critical for induction of autophosphorylation. Its removal abolishes autophosphorylation, but maintains Pbs2-mediated phosphorylation. This 7 amino acids stretch is conserved in the human p38α. Similar to the case of Hog1, it's removal from p38α abolishes p38α's autophosphorylation capability, but maintains, although reduces, its activation by MKK6. This study joins a few recent reports to suggest that, like many protein kinases, MAPKs are also regulated via induced autoactivation.
authors.affiliation: Department of Biological Chemistry, The Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Maayan
authors.forename: Jonah
authors.initials: J
authors.lastname: Beenstock
authors.forename: Irit
authors.initials: I
authors.lastname: Marbach
authors.forename: Shira
authors.initials: S
authors.lastname: Tabachnick
authors.forename: Oded
authors.initials: O
authors.lastname: Livnah
authors.forename: David
authors.initials: D
authors.lastname: Engelberg
mesh_terms: D005656:Fungal Proteins / Q000737:chemistry; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D048669:MAP Kinase Kinase 6 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D009154:Mutation; D009997:Osmotic Pressure; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; C088589:HOG1 protein, S cerevisiae; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6