Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein IkappaBalpha through interaction between the PDZ1 domain and ankyrin repeats.
PTP-BAS is a membrane-associated protein tyrosine phosphatase containing a band-4.1 homology region and five PDZ (PSD-95 Dlg ZO-1) [discs-large homology region ('DHR')/Gly-Leu-Gly-Phe ('GLGF')] domains. The second and fourth PDZ domains were reported to associate with Fas/CD95. By using the first PDZ domain as a bait in yeast two-hybrid screening, we have identified IkappaBalpha as a binding protein. IkappaBalpha associated with PDZ1 through the stretch of the N-terminal three ankyrin repeats. The association was also confirmed in HeLa cells by co-immunoprecipitation experiments. Inhibition of PTP-BAS by expression of dominant-negative PTP-BAS mutant resulted in tyrosine-phosphorylation of IkappaBalpha. Tyrosine-phosphorylation of IkappaBalpha is a key event in activation of nuclear factor (NF)-kappaB during reoxygenation. PTP-BAS may thus play a regulatory role in activation of NF-kappaB under high oxidative stress.
Maekawa
K
K
Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566-0022, Japan. kazuhiko.maekawa@shionogi.co.jp
Imagawa
N
N
Naito
A
A
Harada
S
S
Yoshie
O
O
Takagi
S
S
D017487:Ankyrins / Q000378:metabolism; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012441:Saccharomyces cerevisiae / Q000235:genetics
D017487:Ankyrins; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C033652:postsynaptic density proteins; D000072000:NF-KappaB Inhibitor alpha; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D017027:Protein Tyrosine Phosphatases