title: Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase.
abstract: The p38 mitogen-activated protein kinases (MAPK) are activated by cellular stresses and play an important role in regulating gene expression. We have isolated a cDNA encoding a novel protein kinase that has significant homology (57% amino acid identity) to human p38alpha/CSBP. The novel kinase, p38delta, has a nucleotide sequence encoding a protein of 365 amino acids with a putative TGY dual phosphorylation motif. Dot-blot analysis of p38delta mRNA in 50 human tissues revealed a distribution profile of p38delta that differs from p38alpha. p38delta is highly expressed in salivary gland, pituitary gland, and adrenal gland, whereas p38alpha is highly expressed in placenta, cerebellum, bone marrow, thyroid gland, peripheral leukocytes, liver, and spleen. Like p38alpha, p38delta is activated by cellular stress and proinflammatory cytokines. p38delta phosphorylates ATF-2 and PHAS-I, but not MAPK-activated protein kinase-2 and -3, known in vivo and in vitro substrates of p38alpha. We also observed that p38delta was strongly activated by MKK3 and MKK6, while p38alpha was preferentially activated by MKK6. Other experiments showed that a potent p38alpha kinase inhibitor AMG 2372 minimally inhibited the kinase activity of p38delta. Taken together, these data indicate that p38delta is a new member of the p38 MAPK family and that p38delta likely has functions distinct from that of p38alpha.
authors.affiliation: Amgen Inc., Boulder, Colorado 80301, USA.
authors.forename: X S
authors.initials: XS
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Diener
authors.forename: C L
authors.initials: CL
authors.lastname: Manthey
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: B
authors.initials: B
authors.lastname: Rosenzweig
authors.forename: J
authors.initials: J
authors.lastname: Bray
authors.forename: J
authors.initials: J
authors.lastname: Delaney
authors.forename: C N
authors.initials: CN
authors.lastname: Cole
authors.forename: P Y
authors.initials: PY
authors.lastname: Chan-Hui
authors.forename: N
authors.initials: N
authors.lastname: Mantlo
authors.forename: H S
authors.initials: HS
authors.lastname: Lichenstein
authors.forename: M
authors.initials: M
authors.lastname: Zukowski
authors.forename: Z
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases