Protein kinase a suppresses antiproliferative effect of interferon-α in hepatocellular carcinoma by activation of protein tyrosine phosphatase SHP2.

ABSTRACT: Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) plays a dual role in cancer initiation and progression. Identifying signals that modulate the function of SHP2 can improve current therapeutic approaches for IFN-α/β in HCC. We showed that cAMP-dependent PKA suppresses IFN-α/β-induced JAK/STAT signaling by increasing the phosphatase activity of SHP2, promoting the dissociation of SHP2 from the receptor for activated C-kinase 1 (RACK1) and binding to STAT1. Additionally, cAMP-degrading phosphodiesterase 4D (PDE4D) physically interacts with RACK1 to regulate PKA-mediated SHP2 activity and STAT1 phosphorylation. IFN-α activates PKA by inducing the expression of cyclooxygenase 2 (COX2) and the production of prostaglandin E₂ (PGE₂), which in turn stimulates th

SUBMITTER: Sheng Y 

PROVIDER: S-EPMC11849638 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature