TAB1beta (transforming growth factor-beta-activated protein kinase 1-binding protein 1beta ), a novel splicing variant of TAB1 that interacts with p38alpha but not TAK1.
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 p38alpha MAPK can be carried out not only by its upstream MAPK kinases (MKKs) but also by p38alpha autophosphorylation. p38alpha autoactivation requires an interaction of p38alpha with TAB1 (transforming growth factor-beta-activated protein kinase 1-binding protein 1). The autoactivation mechanism of p38alpha 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, TAB1beta. TAB1 and TAB1beta share the first 10 exons. The 11th and 12th exons of TAB1 were spliced out in TAB1beta, and an extra exon, termed exon beta, downstream of exons 11 and 12 in the genome was used as the last exon in TAB1beta. The mRNA of TAB1beta was expressed in all cell lines examined. The TAB1beta 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, TAB1beta interacts with p38alpha but not other MAPKs and stimulates p38alpha autoactivation. Different from TAB1, TAB1beta does not bind or activate TAK1. Inhibition of TAB1beta expression with RNA interference in MDA231 breast cancer cells resulted in the reduction of basal activity of p38alpha and invasiveness of MDA231 cells, suggesting that TauAlphaBeta1beta is involved in regulating p38alpha activity in physiological conditions.
Ge
Baoxue
B
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Xiong
Xinsheng
X
Jing
Qing
Q
Mosley
Jennifer L
JL
Filose
Angela
A
Bian
Dafang
D
Huang
Shuang
S
Han
Jiahuai
J
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004338:Drug Combinations; D004789:Enzyme Activation; D005091:Exons; D020224:Expressed Sequence Tags; D017930:Genes, Reporter; D005822:Genetic Vectors; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011509:Proteoglycans / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003094:Collagen; D018076:DNA, Complementary; D004338:Drug Combinations; D005982:Glutathione Transferase; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D020930:MAP Kinase Kinase Kinases; D048308:Mitogen-Activated Protein Kinase 14; D020928:Mitogen-Activated Protein Kinases; D020033:Protein Isoforms; D011509:Proteoglycans; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000099151:MAP Kinase Kinase Kinase 7; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human; C059485:matrigel