Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta).
Mitogen-activated protein (MAP) kinase cascades represent one of the major signal systems used by eukaryotic cells to transduce extracellular signals into cellular responses. Four MAP kinase subgroups have been identified in humans: ERK, JNK (SAPK), ERK5 (BMK), and p38. Here we characterize a new MAP kinase, p38beta. p38beta is a 372-amino acid protein most closely related to p38. It contains a TGY dual phosphorylation site, which is required for its kinase activity. Like p38, p38beta is activated by proinflammatory cytokines and environmental stress. A comparison of events associated with the activation of p38beta and p38 revealed differences, most notably in the preferred activation of p38beta by MAP kinase kinase 6 (MKK6), whereas p38 was activated nearly equally by MKK3, MKK4, and MKK6. Moreover, in vitro and in vivo experiments showed a strong substrate preference by p38beta for activating transcription factor 2 (ATF2). Enhancement of ATF2-dependent gene expression by p38beta was approximately20-fold greater than that of p38 and other MAP kinases tested. The data reported here suggest that while closely related, p38beta and p38 may be regulated by differing mechanisms and may exert their actions on separate downstream targets.
Jiang
Y
Y
Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
Chen
C
C
Li
Z
Z
Guo
W
W
Gegner
J A
JA
Lin
S
S
Han
J
J
D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000145:classification / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles; D007527:Isoenzymes / Q000235:genetics*; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases / Q000145:classification / Q000235:genetics*; D008969:Molecular Sequence Data; D011725:Pyridines; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014018:Tissue Distribution; D014157:Transcription Factors
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D007093:Imidazoles; D007527:Isoenzymes; D011725:Pyridines; D014157:Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole