Abstract
Dual-specificity phosphatases (DUSPs) have the ability to dephosphorylate both phosphotyrosine and phosphoserine/threonine residues. DUSPs are currently known to be involved in the negative regulation of MAPKs (mitogen-activated protein kinases) signaling pathway and cell cycle transitions. However, there are some small DUSPs whose functions remain unknown. Some DUSPs are called atypical DUSPs, because they contain only the consensus DUSP catalytic domain. DUSP23 contains 151 amino acids with molecular mass of 15~16 kDa, and it’s the smallest atypical DUSPs whose function is unknown. According to a previous, DUSP23 was expressed in most fetal tissues but in only testis and colon during adulthood. According to our microarray, RT-PCR, and Western blotting data, we showed that DUSP23 was transcriptionally inhibited when EGFR or mutant EGFR was overexpressed in H1299 non-small cell lung cancer cell line. Moreover, DUSP23 could reduce EGF-induced activation of EGFR and inhibit Src activity. Protein phosphatase assay showed that EGFR and Src were not direct substrates of DUSP23. As for functional assays, we found that DUSP23 could not alter cell growth and migration, but could affect cell morphology in a 3D culture model. And we found there is no significant correlation between the expression levels of EGFR and DUSP23 in several NSCLC cell lines. These results indicated that DUSP23 might be the negative regulator of EGFR signaling pathway in H1299. However, whether DUSP23 reduces EGF-induced activation of EGFR through the inhibition of Src activity is still under investigation.