Involvement of Hgs/Hrs in signaling for cytokine-mediated c-fos induction through interaction with TAK1 and Pak1

Hgs/Hrs is a tyrosine-phosphorylated FYVE finger protein that is induced by stimulation with various cytokines and growth factors. Here we show that Hgs plays critical roles in the signaling pathway for the interleukin-2. induced activation of the serum-response element and cyclic AMP-response element of the c-fos promoter. We found that Hgs associated physically with transforming growth factor-beta -activated kinase 1 (TAK1) and p21-activated kinase 1 (Pak1), which mediate the activation of c-Jun N-terminal kinase and serum response factor, respectively, leading to transactivation via the serum-response element and cyclic AMP-response element. These results suggest that Hgs is involved in the TAK1-JNK and Pak1-serum response factor pathways for the c-fos induction that is initiated by cytokines.