{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:57:37Z","timestamp":1790009857531,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,5,9]],"date-time":"2007-05-09T00:00:00Z","timestamp":1178668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2007,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mast cells proliferate in vivo in areas of active fibrosis, during parasite infestations, in response to repeated immediate hypersensitivity reactions and in patients with mastocytosis. We investigated how progesterone reduces the proliferation of HMC\u20101<jats:sup>560<\/jats:sup> mast cells that proliferate spontaneously in culture. Cells were incubated with 1 \u00b5M to 1 nM progesterone for 24\u201348 h. Progesterone (1 \u00b5M) reduced the spontaneous proliferation of HMC\u20101<jats:sup>560<\/jats:sup> mast cells to half that of cells cultured without hormone. [<jats:sup>3<\/jats:sup>H] thymidine incorporation was only 50% of control; there were fewer cells in G2\/M and more cells in G0\/G1. The amounts of phospho\u2010Raf\u20101 (Tyr 340\u2013341) and phospho\u2010p42\/p44 MAPK proteins were also reduced. In contrast progesterone had no effect on MAP kinase\u2010phosphatase\u20101. The Raf\/MAPK pathway, which depends on Src kinase activity, is implicated in the control of cell proliferation. HMC\u20101<jats:sup>560<\/jats:sup> cells incubated with the tyrosine kinase inhibitor PP1 proliferated more slowly than controls and had less phospho\u2010Raf\u20101 (Tyr 340\u2013341) and phospho\u2010p42\/p44 MAPK. The Csk homologous kinase (CHK), an endogenous inhibitor of Src protein tyrosine kinases, was also enhanced in progesterone\u2010treated cells. In contrast, progesterone had no effect on the growth of cells transfected with siRNA CHK. We conclude that progesterone increases the amount of csk homologous kinase, which in turn reduces HMC\u20101<jats:sup>560<\/jats:sup> mast cell proliferation. This effect parallels decreases in the phosphorylated forms of Raf\u20101 and p42\/44 MAPK, as their production depends on Src kinase activity. J. Cell. Biochem. 102: 1271\u20131280, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.21357","type":"journal-article","created":{"date-parts":[[2007,5,9]],"date-time":"2007-05-09T18:45:18Z","timestamp":1178736318000},"page":"1271-1280","source":"Crossref","is-referenced-by-count":8,"title":["Progesterone increases csk homologous kinase in HMC\u20101<sup>560<\/sup> human mast cells and reduces cell proliferation"],"prefix":"10.1002","volume":"102","author":[{"given":"Marie\u2010Pierre","family":"Belot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Latifa","family":"Abdennebi\u2010Najar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Gaudin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Emilie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Machelon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,5,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/rp.56.1.127"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-8244(03)00202-5"},{"key":"e_1_2_5_4_1","first-page":"305","article-title":"Src family kinase activity is required for Kit\u2010mediated mitogen\u2010activated protein (MAP) kinase activation, however loss of functional retinoblastoma protein makes MAP kinase activation unnecessary for growth of small cell lung cancer cells","volume":"11","author":"Bondzi C","year":"2000","journal-title":"Cell Growth Differ"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.120524"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0145-2126(88)90050-1"},{"key":"e_1_2_5_7_1","first-page":"33","article-title":"Mastocytosis: classification, diagnosis, and clinical presentation","volume":"25","author":"Castells MC","year":"2004","journal-title":"Allergy Asthma Proc"},{"key":"e_1_2_5_8_1","first-page":"3437","article-title":"Two distinct protein isoforms are encoded by ntk, a csk\u2010related tyrosine protein kinase gene","volume":"9","author":"Chow LM","year":"1994","journal-title":"Oncogene"},{"key":"e_1_2_5_9_1","first-page":"881","article-title":"Progesterone inhibits human endometrial cancer cell growth and invasiveness: down\u2010regulation of cellular adhesion molecules through progesterone B receptors","volume":"62","author":"Dai D","year":"2002","journal-title":"Cancer Res"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.08.084"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.18.4.502"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-5-3-435"},{"key":"e_1_2_5_13_1","first-page":"183","article-title":"Effects of hormones on the number, distribution and degranulation of mast cells in the ovarian complex of mice","volume":"84","author":"Jaiswal K","year":"1996","journal-title":"Acta Physiol Hung"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod53.2.312"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/00016347109157335"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.7108"},{"key":"e_1_2_5_17_1","first-page":"1636","article-title":"High\u2010intensity Raf signals convert mitotic cell cycling into cellular growth","volume":"58","author":"Kerkhoff E","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000236929"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202929"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0117"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0732"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410X.1996.08178.x"},{"key":"e_1_2_5_23_1","first-page":"395","article-title":"Progestins inhibit the growth of MDA\u2010MB\u2010231 cells transfected with progesterone receptor complementary DNA","volume":"5","author":"Lin VC","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.43.27450"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(01)00039-X"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.13.7557021"},{"key":"e_1_2_5_27_1","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1016\/S0021-9258(17)40458-3","article-title":"Steroid hormone receptors in normal human lymphocytes. 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