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

European Journal of Biochemistry
France DemaugreChristian Bréchot

Abstract

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 RII alpha regulatory subunit of cAMP-dependent protein kinase (PKA) as a partner of HIP/PAP. HIP/PAP and RII alpha 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 sugge...Continue Reading

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Citations

May 13, 2009·Cellular and Molecular Life Sciences : CMLS·M Ferrés-MasóE Folch-Puy
Aug 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hanh-Tu LieuLaurence Christa
Mar 31, 2015·The Cancer Journal·David Y LewisKevin M Brindle
Dec 29, 2006·Diabetes·Werner GurrRobert Sherwin
Nov 29, 2013·Journal of Labelled Compounds & Radiopharmaceuticals·Nashaat TurkmanMian M Alauddin

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