RRC ID 30906
Author Sudo T, Yagasaki Y, Hama H, Watanabe N, Osada H.
Title Exip, a new alternative splicing variant of p38 alpha, can induce an earlier onset of apoptosis in HeLa cells.
Journal Biochem. Biophys. Res. Commun.
Abstract One of the major families of the mitogen-activated kinases (MAPK), p38, has been shown to transduce extracellular stress stimuli into cellular responses. Among them, p38 alpha is the best characterized isoform and many biological phenomena, especially in the inflammatory responses, were attributed to the specific inhibitor-sensitive isoforms, namely p38 alpha and p38 beta. However, the roles played by each member are still unclear. Here, we report the identification of a new splice variant of p38 alpha, Exip (for exon skip), by RT-PCR using mRNA derived from a renal tumor cell line, OS-RC-2. Exip is predicted to encode a 307-amino-acid protein and the absence of exons 10, 11, and 11' results in the shift of the reading frame at the exon 9-12 junction to produce a unique 53-amino-acid C-terminus. The expression of mRNA was barely observed in cultured cells tested, but substantial amounts of mRNA were detected in mouse tissues. Unlike p38 alpha, Exip lost a common docking domain well conserved in major MAPK families for their specific interactions with upstream kinases or downstream substrates. Even though Exip is not phosphorylated at conserved TGY motif by p38-activating treatments, such as an osmotic shock or coexpression with a constitutive active form of MKK6 in HeLa cells, Exip can induce an earlier onset of apoptosis in HeLa cells. These results indicate that Exip has unique properties as a member of p38 alpha and may play role(s) in the signal transduction pathway(s) different from those of p38 alpha.
Volume 291(4)
Pages 838-43
Published 2002-3-8
DOI 10.1006/bbrc.2002.6529
PII S0006291X02965290
PMID 11866441
MeSH 3T3 Cells Alternative Splicing* Amino Acid Sequence Animals Apoptosis* Base Sequence Calcium-Calmodulin-Dependent Protein Kinases / metabolism Cloning, Molecular HeLa Cells Humans Kinetics MAP Kinase Kinase 6 Mice Microscopy, Fluorescence Mitogen-Activated Protein Kinase 14 Mitogen-Activated Protein Kinases / genetics* Mitogen-Activated Protein Kinases / pharmacology* Mitogen-Activated Protein Kinases / physiology Molecular Sequence Data Protein Isoforms / genetics Protein Isoforms / physiology RNA, Messenger / biosynthesis Tissue Distribution Tumor Cells, Cultured
IF 2.559
Times Cited 15
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material pcDNA3Flag-hp38 (RDB08166) pcDNA3HA-hp38 (RDB08167) pEGFP-hp38alpha (RDB08179) pcDNA3Flag-hExip (RDB08182) pcDNA3HA-hExip (RDB08183) pEGFP-hExip (RDB08188) pcDNA3Flag-MKK6 (RDB08209) pcDNA3Flag-MKK6D/D (RDB08210)