TAILIEUCHUNG - Báo cáo khoa học: HIP/PAP, a C-type lectin overexpressed in hepatocellular carcinoma, binds the RIIa regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signalling

HIP/PAP is a C-type lectin overexpressed in hepatocel-lular 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 RIIa regulatory subunit of cAMP-dependent protein kinase (PKA) as a partner of HIP/PAP. HIP/PAP and RIIa were coimmunoprecipi-tated in HIP/PAP expressing cells. . | Eur. J. Biochem. 271 3812-3820 2004 FEBS 2004 doi HIP PAP a C-type lectin overexpressed in hepatocellular carcinoma binds the RIIa regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signalling France Demauare1 Yannick PhilĨDDe1 Sokavuth Sar1. Bernard Pileire2 Laurence Christa1 Chantal Lasserre1 and Christian Brechot1 1INSERM U370 CHU Necker Enfants Malades Paris France laboratory of Biochemistry CHU Antilles-Guyane Point à Pitre Guadeloupe France 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 RIIa regulatory subunit of cAMP-dependent protein kinase PKA as a partner of HIP PAP. HIP PAP and RIIa 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. Keywords C-type lectin HIP PAP PKA phosphorylation liver. The HIP PAP-encoding gene has been shown to be overexpressed in human hepatocellular carcinoma HCC 1 and in the .

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