Alternative titles; symbols
HGNC Approved Gene Symbol: MAPK11
Cytogenetic location: 22q13.33 Genomic coordinates (GRCh38): 22:50,263,713-50,270,380 (from NCBI)
Mitogen-activated protein kinase (MAPK) cascades represent one of the major signal systems used by eukaryotic cells to transduce extracellular signals into cellular responses. Four MAPK subgroups have been identified in humans: the extracellular signal-regulated kinases (ERKs), the c-Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPKs), the ERK5/BMK protein (602521), and the p38 MAP kinases. MAPKs are activated by dual-specificity MAPK kinases (MAPKKs; see 602425).
By BLAST searching of an EST database, Jiang et al. (1996) identified a sequence that was similar to that of p38 (600289). Using the corresponding cDNA to screen a placenta library, they isolated cDNAs encoding a protein that they designated p38-beta. Stein et al. (1997) and Enslen et al. (1998) also identified cDNAs encoding p38-beta, which they designated p38-2 and p38-beta-2, respectively. Jiang et al. (1996) reported that the predicted protein sequence of p38-beta is approximately 74% identical to that of p38, and 40 to 50% identical to those of other MAPKs. Both p38 and p38-beta contain a unique TGY dual phosphorylation motif. Using mammalian cells expressing p38-beta, Jiang et al. (1996) demonstrated that, like p38, it is activated by proinflammatory cytokines and environmental stress. The MAPKK MKK6 (601254) preferentially activated p38-beta. In vitro and in vivo experiments showed that p38-beta has a strong substrate preference for ATF2 (CREB2; 123811). In extracts of cells expressing epitope-tagged p38-beta, the protein had a mass of approximately 42 kD. Northern blot analysis revealed that p38-beta is expressed as a 2.5-kb mRNA in various tissues. By analysis of Northern blots and of multiple cDNAs, both Stein et al. (1997) and Jiang et al. (1996) found evidence of incompletely spliced transcripts. Using RT-PCR, Stein et al. (1997) determined that in some cell lines, up to 50% of the mRNA has introns.
Stein et al. (1997) and Enslen et al. (1998) reported that the p38-beta protein is 364 amino acids in length and is missing an 8-amino acid insertion present in the sequence reported by Jiang et al. (1996). Rasooly (1998) noted that the 2 isoforms appear to result from alternative splicing (GenBank 2072361, 2499603). Enslen et al. (1998) determined that the longer isoform had no activity in vitro or in vivo, in contradiction to the studies of Jiang et al. (1996).
Enslen, H., Raingeaud, J., Davis, R. J. Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. J. Biol. Chem. 273: 1741-1748, 1998. [PubMed: 9430721] [Full Text: https://doi.org/10.1074/jbc.273.3.1741]
Jiang, Y., Chen, C., Li, Z., Guo, W., Gegner, J. A., Lin, S., Han, J. Characterization of the structure and function of a new mitogen-activated protein kinase (p38-beta). J. Biol. Chem. 271: 17920-17926, 1996. [PubMed: 8663524] [Full Text: https://doi.org/10.1074/jbc.271.30.17920]
Rasooly, R. S. Personal Communication. Baltimore, Md. 6/15/1998.
Stein, B., Yang, M. X., Young, D. B., Janknecht, R., Hunter, T., Murray, B. W., Barbosa, M. S. p38-2, a novel mitogen-activated protein kinase with distinct properties. J. Biol. Chem. 272: 19509-19517, 1997. [PubMed: 9235954] [Full Text: https://doi.org/10.1074/jbc.272.31.19509]