TAB1β (transforming growth factor-β-activated protein kinase 1-binding protein 1β), a novel splicing variant of TAB1 that interacts with p38α but not TAK1

Baoxue Ge, Xinsheng Xiong, Qing Jing, Jennifer L. Mosley, Angela Filose, Dafang Bian, Shuang Huang, Jiahuai Han

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The mitogen-activated protein kinases (MAPKs) play an important role in a variety of biological processes. Activation of MAPKs is mediated by phosphorylation on specific regulatory tyrosine and threonine sites. We have recently found that activation of p38α MAPK can be carried out not only by its upstream MAPK kinases (MKKs) but also by p38α autophosphorylation. p38α autoactivation requires an interaction of p38α with TAB1 (transforming growth factor-β-activated protein kinase 1-binding protein 1). The autoactivation mechanism of p38α has been found to be important in cellular responses to a number of physiologically relevant stimuli. Here, we report the characterization of a splicing variant of TAB1, TAB1β. TAB1 and TABiβ share the first 10 exons. The 11th and 12th exons of TAB1 were spliced out in TAB1β, and an extra exon, termed exon β, downstream of exons 11 and 12 in the genome was used as the last exon in TAB1β. The mRNA of TAB1β was expressed in all cell lines examined. The TAB1β mRNA encodes a protein with an identical sequence to TAB1 except the C-terminal 69 amino acids were replaced with an unrelated 27-amino acid sequence. Similar to TAB1, TAB1β interacts with p38α but not other MAPKs and stimulates p38α autoactivation. Different from TAB1, TAB1β does not bind or activate TAK1. Inhibition of TAB1β expression with RNA interference in MDA231 breast cancer cells resulted in the reduction of basal activity of p38α and invasiveness of MDA231 cells, suggesting that TAB1β is involved in regulating p38α activity in physiological conditions.

Original languageEnglish (US)
Pages (from-to)2286-2293
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number4
DOIs
StatePublished - Jan 24 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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