Association of protein-tyrosine phosphatase PTP-BAS with the transcription-factor-inhibitory protein I kappa-B alpha 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 Dig ZO-1) [discs-large homolo gy 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 PD Z domain as a bait in yeast two-hybrid screening, we have identified I kapp a B alpha as a binding protein. I kappa-B alpha associated with PDZ1 throug h the stretch of the N-terminal three ankyrin repeats. The association was also confirmed in HeLa cells by co-immunoprecipitation experiments. Inhibit ion of PTP-BAS by expression of dominant-negative PTP-BAS mutant resulted i n tyrosine-phosphorylation of I kappa-B alpha. Tyrosine-phosphorylation of I kappa-B alpha is a key evens in activation of nuclear factor (NF)-kappa B during reoxygenation. PTP-BAS may thus play a regulatory role in activatio n of NF-kappa B under high oxidative stress.