{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:05:36Z","timestamp":1791219936142,"version":"4.1.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,7,7]]},"abstract":"<jats:p>Expression of the pre-B cell receptor (pre-BCR) leads to activation of the adaptor molecule SLP-65 and the cytoplasmic kinase Btk. Mice deficient for one of these signaling proteins have an incomplete block in B cell development at the stage of large cycling pre-BCR+CD43+ pre-B cells. Our recent findings of defective SLP-65 expression in \u223c50% of childhood pre-B acute lymphoblastic leukemias and spontaneous pre-B cell lymphoma development in SLP-65\u2212\/\u2212 mice demonstrate that SLP-65 acts as a tumor suppressor. To investigate cooperation between Btk and SLP-65, we characterized the pre-B cell compartment in single and double mutant mice, and found that the two proteins have a synergistic role in the developmental progression of large cycling into small resting pre-B cells. We show that Btk\/SLP-65 double mutant mice have a dramatically increased pre-B cell tumor incidence (\u223c75% at 16 wk of age), as compared with SLP-65 single deficient mice (&amp;lt;10%). These findings demonstrate that Btk cooperates with SLP-65 as a tumor suppressor in pre-B cells. Furthermore, transgenic low-level expression of a constitutive active form of Btk, the E41K-Y223F mutant, prevented tumor formation in Btk\/SLP-65 double mutant mice, indicating that constitutive active Btk can substitute for SLP-65 as a tumor suppressor.<\/jats:p>","DOI":"10.1084\/jem.20030615","type":"journal-article","created":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:25:43Z","timestamp":1057019143000},"page":"91-98","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Bruton's Tyrosine Kinase Cooperates with the B Cell Linker Protein SLP-65 as a Tumor Suppressor in Pre-B Cells"],"prefix":"10.1084","volume":"198","author":[{"given":"Rogier","family":"Kersseboom","sequence":"first","affiliation":[{"name":"1Department of Immunology, Erasmus MC Rotterdam, P.O. 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