Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Burnatowska-Hledin, M. et al.

Burnatowska-Hledin, Zhao, Capps, Poel, Parmelee, Mungall, Sharangpani, Listenberger,

VACM-1, a cullin gene family member, regulates cellular signaling.

Vasopressin-activated Ca(2+)-mobilizing (VACM-1) receptor binds arginine vasopressin (AVP) but does not have amino acid sequence homology with the traditional AVP receptors. VACM-1, however, is homologous with a newly discovered cullin family of proteins that has been implicated in the regulation of cell cycle through the ubiquitin- mediated degradation of cyclin-dependent kinase inhibitors. Because cell cycle processes can be regulated by the transmembrane signal transduction systems, the effects of VACM-1 expression on the Ca(2+) and cAMP-dependent signaling pathway were examined in a stable cell line expressing VACM-1 in VACM-1 transfected COS-1 cells and in cells cotransfected with VACM-1 and the adenylyl cyclase- linked V(2) AVP receptor cDNAs. Expression of the VACM-1 gene reduced basal as well as forskolin- and AVP-stimulated cAMP production. In cells cotransfected with VACM-1 and the V(2) receptor, the AVP- and forskolin-induced increases in adenylyl cyclase activity and cAMP production were inhibited. The inhibitory effect of VACM-1 on cAMP production could be reversed by pretreating cells with staurosporin, a protein kinase A (PKA) inhibitor, or by mutating S730A, the PKA-dependent phosphorylation site in the VACM-1 sequence. The protein kinase C specific inhibitor GÃ¶-6983 further enhanced the inhibitory effect of VACM-1 on AVP-stimulated cAMP production. Finally, AVP stimulated D-myo-inositol 1,4, 5-trisphosphate production both in the transiently transfected COS-1 cells and in the stable cell line expressing VACM-1, but not in the control COS-1 and Chinese hamster ovary cells. Our data demonstrate that VACM-1, the first mammalian cullin protein to be characterized, is involved in the regulation of signaling.[1]

References

VACM-1, a cullin gene family member, regulates cellular signaling. Burnatowska-Hledin, M., Zhao, P., Capps, B., Poel, A., Parmelee, K., Mungall, C., Sharangpani, A., Listenberger, L. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]

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