HIP/PAP, a C‐type lectin overexpressed in hepatocellular carcinoma, binds the RIIα regulatory subunit of cAMP‐dependent protein kinase and alters the cAMP‐dependent protein kinase signalling

HIP/PAP is a C‐type lectin overexpressed in hepatocellular carcinoma (HCC). Pleiotropic biological activities have been ascribed to this protein, but little is known about the function of HIP/PAP in the liver. In this study, therefore, we searched for proteins interacting with HIP/PAP by screening a...

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Veröffentlicht in:European journal of biochemistry 2004-10, Vol.271 (19), p.3812-3820
Hauptverfasser: Demaugre, France, Philippe, Yannick, Sar, Sokavuth, Pileire, Bernard, Christa, Laurence, Lasserre, Chantal, Brechot, Christian
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Sprache:eng
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Zusammenfassung:HIP/PAP is a C‐type lectin overexpressed in hepatocellular carcinoma (HCC). Pleiotropic biological activities have been ascribed to this protein, but little is known about the function of HIP/PAP in the liver. In this study, therefore, we searched for proteins interacting with HIP/PAP by screening a HCC cDNA expression library. We have identified the RIIα regulatory subunit of cAMP‐dependent protein kinase (PKA) as a partner of HIP/PAP. HIP/PAP and RIIα were coimmunoprecipitated in HIP/PAP expressing cells. The biological relevance of the interaction between these proteins was established by demonstrating, using fractionation methods, that they are located in a same subcellular compartment. Indeed, though HIP/PAP is a protein secreted via the Golgi apparatus we showed that a fraction of HIP/PAP escaped the secretory apparatus and was recovered in the cytosol. Basal PKA activity was increased in HIP/PAP expressing cells, suggesting that HIP/PAP may alter PKA signalling. Indeed, we showed, using a thymidine kinase‐luciferase reporter plasmid in which a cAMP responsive element was inserted upstream of the thymidine kinase promoter, that luciferase activity was enhanced in HIP/PAP expressing cells. Thus our findings suggest a novel mechanism for the biological activity of the HIP/PAP lectin.
ISSN:0014-2956
1432-1033
DOI:10.1111/j.1432-1033.2004.04302.x