Jean-Pierre Kinet, MD
Beth Israel Deaconess Medical Center
330 Brookline Ave.
Boston, MA 02215
Our laboratory is interested in two separate but related questions:
The role of mast cells and their receptors in inflammation. The mechanisms of calcium mobilization in cells of the immune system, including mast cells, and the biological consequences of the calcium signals. The laboratory is analyzing these questions by combining a variety of approaches including molecular biology and genetics, biochemistry and cell biology. Research in my laboratory led to the identification of CRACM1/Ora 1 as an essential protein for store-operated Ca2+ influx and as a component of the CRAC channel. Subsequent studies have shown that CRACM1 forms multimeric assemblies that bind STIM1, an ER Ca2+ sensor, and that acidic residues in the transmembrane and extracellular domains of CRACM1 contribute to the ionic selectivity of the CRAC-channel pore. Following these studies our laboratory has embarked in the identifications of other novel channels in cells of the immune system. These studies are currently ongoing.
Kraft S, Jouvin M-H, Kulkarni N, Kissing S, Morgan ES, Dvorak AM, Schröder B, Saftig P, and Kinet J-P The tetraspanin CD63 is required for efficient IgE-mediated mast cell degranulation and anaphylaxis. J. Immunol. 2013 Aug 14. [Epub ahead of print]
Gomez-Ospina N, Panagiotakos G, Portmann T, Pasca SP, Rabah D, Budzillo A, Kinet J-P, Dolmetsch RE. A Promoter in the Coding Region of the Calcium Channel Gene CACNA1C Generates the Transcription Factor CCAT. PLoS One. 2013 Apr 16;8(4)
Vig, M., Dehaven, W.I., Bird, G.S., Billingsley, J.M., Wang, H., Rao, P.E., Hutchings, A.B., Jouvin, M.-H., Putney, J.W., Kinet, J.-P. A major defect in mast cell effector functions in CRACM1-/- mice. Nat Immunol. 2008 Jan;9(1):89-96. Epub 2007 Dec 2.
Peinelt C., Vig M., Koomoa D. L., Beck A., Nadler M., Koblan-Huberson M., Lis A., Andrea Fleig A., Penner R., & Kinet J.-P. Amplification of Ca2 Release-Activated Ca2 (CRAC) current by STIM1 and CRACM1 (ORAI1). Nature Cell Biol. 8:771-773, 2006
Vig, M., Peinelt, C., Beck, A., Koomoa, D. L., Rabah, D., Koblan-Huberson, M., Kraft, S., Turner, H., Fleig, A., Penner, R., Kinet, J.-P. CRACM1 is a plasma membrane protein essential for store-operated Ca2 entry. Science 312:1220-1223, 2006
Last Update: 1/6/2014