The MEK kinases MEKK4/Ssk2p facilitate complexity in the stress signaling responses of diverse systems.
The mammalian JNK/p38 MAP kinase kinase kinase MEKK4 and the Saccharomyces cerevisiae Ssk2p are highly homologous. MEKK4 can replace all of the known functions of Ssk2p in yeast, including functioning in the high osmolarity glycerol (HOG) MAPK pathway and the recently described actin recovery pathway. MEKK4 and Ssk2p share a number of conserved domains and appear to be activated by a similar mechanism. Binding of an activating protein to the N-terminal region alleviates auto-inhibition and causes the kinase to auto-phosphorylate, resulting in activation. In this review we will examine the role of the MAP kinase kinase kinase isoform Ssk2p/MEKK4 in the adaptation of both yeast and mammalian systems to specific external stimuli. Recent work has provided a wealth of information about the activation, regulation, and functions of these MEKK kinases to extra-cellular signals. We will also highlight evidence supporting a role for MEKK4 in mediating actin recovery following osmotic shock in mammalian cells.
Bettinger
Blaine T
BT
Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 E. Adams St., Syracuse, New York 13210, USA.
Amberg
David C
DC
D000199:Actins / Q000378:metabolism; D000222:Adaptation, Physiological; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D005544:Forecasting; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D048768:MAP Kinase Kinase Kinase 4 / Q000737:chemistry / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases; D008322:Mammals; D008969:Molecular Sequence Data; D009997:Osmotic Pressure; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
D000199:Actins; D007527:Isoenzymes; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; D048768:MAP Kinase Kinase Kinase 4; D020930:MAP Kinase Kinase Kinases; C472815:SSK2 protein, S cerevisiae