RRC ID 28682
Author Yagasaki Y, Sudo T, Osada H.
Title Exip, a splicing variant of p38alpha, participates in interleukin-1 receptor proximal complex and downregulates NF-kappaB pathway.
Journal FEBS Lett
Abstract The members of the p38 mitogen-activated protein kinase, especially specific inhibitors such as SB203580 sensitive isoforms, have been shown to play important roles in immune responses as well as in many biological events. In the course of our study to understand how p38 can be responsible for numerous biological phenomena, we have recently identified Exip, an alternative splicing variant of p38alpha. Exip retains amino acids responsible for the sensitivity to SB203580. Exip may also be involved in the intracellular signal transduction pathway different from those of conventional p38s. Though Exip is less abundant, it may play a critical role under certain circumstances. Here we report that Exip, but not p38alpha, binds to Toll interacting protein which is involved in interleukin-1 (IL-1) signaling pathway as a component of the receptor proximal complex and impaired NF-kappaB activity. Moreover, Exip binds to another component of the complex, IL-1 associating kinase. Exogenous-expression of Exip resulted in downregulation of NF-kappaB activities both in HeLa and HEK293T cells. Together, these results demonstrate that Exip can be a new component of NF-kappaB pathway, and contribute to a comprehensive understanding of the signal transduction pathway in the inflammatory responses.
Volume 575(1-3)
Pages 136-40
Published 2004-9-24
DOI 10.1016/j.febslet.2004.08.050
PII S0014579304010695
PMID 15388348
MeSH Alternative Splicing* Cell Line Down-Regulation* Enzyme Inhibitors / metabolism Humans Imidazoles / metabolism Interleukin-1 Receptor-Associated Kinases Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors Mitogen-Activated Protein Kinase 14 / genetics* Mitogen-Activated Protein Kinase 14 / metabolism* NF-kappa B / metabolism* Protein Binding Protein Kinases / metabolism Pyridines / metabolism Receptors, Interleukin-1 / metabolism* Signal Transduction / physiology Two-Hybrid System Techniques
IF 3.057
Times Cited 12
DNA material pcDNA3HA-Tollip (RDB08208)