Integrated Phosphoproteomics for Identifying Substrates of Human Protein Kinase A (PRKACA) and Its Oncogenic Mutant DNAJB1-PRKACA.

ABSTRACT: The DNAJB1-PRKACA fusion is the signature genetic event of fibrolamellar hepatocellular carcinoma (FL-HCC), a rare but lethal liver cancer that primarily affects adolescents and young adults. A deletion fuses the first exon of the HSP40 gene (DNAJB1), with exons 2-10 of protein kinase A (PRKACA), producing the chimeric kinase DNAJB1-PKA_ca (J-PKA_ca). The HSP40 portion's scaffolding/chaperone function has been implicated in redirecting substrate recognition to upregulate oncogenic pathways, but the direct substrates of this fusion are not fully known. We integrated cell-based and in vitro phosphoproteomics to identify substrates targeted directly by PKA and J-PKA_ca, comparing phosphoproteome profiles from cells with in vitro

SUBMITTER: Karamafrooz A 

PROVIDER: S-EPMC10153428 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature