{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T10:29:03Z","timestamp":1794047343305,"version":"4.8.0"},"reference-count":41,"publisher":"Ferrata Storti Foundation (Haematologica)","issue":"2","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["haematol"],"abstract":"<jats:p>Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS\/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and I\u03baB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.<\/jats:p>","DOI":"10.3324\/haematol.2019.225573","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T15:45:22Z","timestamp":1579794322000},"page":"424-436","source":"Crossref","is-referenced-by-count":7,"title":["Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress"],"prefix":"10.3324","volume":"106","author":[{"family":"Michiko Ichii","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Kenji Oritani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Jun Toda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Hideaki Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Henyun Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Hirohiko Shibayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Daisuke Motooka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Yuichi Kitai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Ryuta Muromoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Jun-ichi Kashiwakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Kodai Saitoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Daisuke Okuzaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Tadashi Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Yuzuru Kanakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1856","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"19979","doi-asserted-by":"crossref","unstructured":"Haas S, Trumpp A, Milsom MD. Causes and consequences of hematopoietic stem cell heterogeneity. Cell Stem Cell. 2018; 22(5):627-638.","DOI":"10.1016\/j.stem.2018.04.003"},{"key":"19980","doi-asserted-by":"crossref","unstructured":"Laurenti E, Gottgens B. From haematopoietic stem cells to complex differentiation landscapes. Nature. 2018; 553(7689):418-426.","DOI":"10.1038\/nature25022"},{"key":"19981","doi-asserted-by":"crossref","unstructured":"Pietras EM. Inflammation: a key regulator of hematopoietic stem cell fate in health and disease. Blood. 2017; 130(15):1693-1698.","DOI":"10.1182\/blood-2017-06-780882"},{"key":"19982","doi-asserted-by":"crossref","unstructured":"Baldridge MT, King KY, Goodell MA. Inflammatory signals regulate hematopoietic stem cells. Trends Immunol. 2011; 32(2):57-65.","DOI":"10.1016\/j.it.2010.12.003"},{"key":"19983","doi-asserted-by":"crossref","unstructured":"Zhao JL, Ma C, O'Connell RM. Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell. 2014; 14(4):445-459.","DOI":"10.1016\/j.stem.2014.01.007"},{"key":"19984","doi-asserted-by":"crossref","unstructured":"Liu A, Wang Y, Ding Y, Baez I, Payne KJ, Borghesi L. Cutting edge: hematopoietic stem cell expansion and common lymphoid progenitor depletion require hematopoieticderived, cell-autonomous TLR4 in a model of chronic endotoxin. J Immunol. 2015; 195(6):2524-2528.","DOI":"10.4049\/jimmunol.1501231"},{"key":"19985","doi-asserted-by":"crossref","unstructured":"Nagai Y, Garrett KP, Ohta S. Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity. 2006; 24(6):801-812.","DOI":"10.1016\/j.immuni.2006.04.008"},{"key":"19986","doi-asserted-by":"crossref","unstructured":"Esplin BL, Shimazu T, Welner RS. Chronic exposure to a TLR ligand injures hematopoietic stem cells. J Immunol. 2011; 186(9):5367-5375.","DOI":"10.4049\/jimmunol.1003438"},{"key":"19987","doi-asserted-by":"crossref","unstructured":"Pietras EM, Mirantes-Barbeito C, Fong S. Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat Cell Biol. 2016; 18(6):607-618.","DOI":"10.1038\/ncb3346"},{"key":"19988","doi-asserted-by":"crossref","unstructured":"Matatall KA, Jeong M, Chen S. Chronic infection depletes hematopoietic stem cells through stress-induced terminal differentiation. Cell Rep. 2016; 17(10):2584-2595.","DOI":"10.1016\/j.celrep.2016.11.031"},{"key":"19989","doi-asserted-by":"crossref","unstructured":"Ogonek J, Kralj Juric M, Ghimire S. Immune reconstitution after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016; 7:507.","DOI":"10.3389\/fimmu.2016.00507"},{"key":"19990","doi-asserted-by":"crossref","unstructured":"Pietras EM, Reynaud D, Kang YA. Functionally distinct subsets of lineagebiased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell. 2015; 17(1):35-46.","DOI":"10.1016\/j.stem.2015.05.003"},{"key":"19991","doi-asserted-by":"crossref","unstructured":"Karigane D, Kobayashi H, Morikawa T. p38alpha activates purine metabolism to initiate hematopoietic stem\/progenitor cell cycling in response to stress. Cell Stem Cell. 2016; 19(2):192-204.","DOI":"10.1016\/j.stem.2016.05.013"},{"key":"19992","doi-asserted-by":"crossref","unstructured":"Minoguchi M, Minoguchi S, Aki D. STAP-2\/BKS, an adaptor\/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif. J Biol Chem. 2003; 278(13):11182-11189.","DOI":"10.1074\/jbc.M211230200"},{"key":"19993","doi-asserted-by":"crossref","unstructured":"Muraoka D, Seo N, Hayashi T. Signaltransducing adaptor protein-2 promotes generation of functional long-term memory CD8+ T cells by preventing terminal effector differentiation. Oncotarget. 2017; 8(19):30766-30780.","DOI":"10.18632\/oncotarget.15403"},{"key":"19994","doi-asserted-by":"crossref","unstructured":"Sekine Y, Yumioka T, Yamamoto T. Modulation of TLR4 signaling by a novel adaptor protein signal-transducing adaptor protein-2 in macrophages. J Immunol. 2005; 176(1):380-389.","DOI":"10.4049\/jimmunol.176.1.380"},{"key":"19995","doi-asserted-by":"crossref","unstructured":"Sekine Y, Ikeda O, Tsuji S. Signal-transducing adaptor protein-2 regulates stromal cell-derived factor-1 alpha-induced chemotaxis in T cells. J Immunol. 2009; 183(12):7966-7974.","DOI":"10.4049\/jimmunol.0902096"},{"key":"19996","doi-asserted-by":"crossref","unstructured":"Sekine Y, Nishida K, Yamasaki S. Signal-transducing adaptor protein-2 controls the IgE-mediated, mast cell-mediated anaphylactic responses. J Immunol. 2014; 192(8):3488-3495.","DOI":"10.4049\/jimmunol.1300886"},{"key":"19997","doi-asserted-by":"crossref","unstructured":"Takaki S, Tezuka Y, Sauer K. Impaired lymphopoiesis and altered B cell subpopulations in mice overexpressing Lnk adaptor protein. J Immunol. 2003; 170(2):703-710.","DOI":"10.4049\/jimmunol.170.2.703"},{"key":"19998","doi-asserted-by":"crossref","unstructured":"Fujisawa M, Sakata-Yanagimoto M, Nishizawa S. Activation of RHOAVAV1 signaling in angioimmunoblastic Tcell lymphoma. Leukemia. 2018; 32(3):694-702.","DOI":"10.1038\/leu.2017.273"},{"key":"19999","doi-asserted-by":"crossref","unstructured":"Sekine Y, Ikeda O, Mizushima A. STAP-2 interacts with and modulates BCRABL- mediated tumorigenesis. Oncogene. 2012; 31(40):4384-4396.","DOI":"10.1038\/onc.2011.604"},{"key":"20000","doi-asserted-by":"crossref","unstructured":"Ikeda O, Sekine Y, Mizushima A. Interactions of STAP-2 with Brk and STAT3 participate in cell growth of human breast cancer cells. J Biol Chem. 2010; 285(49):38093-38103.","DOI":"10.1074\/jbc.M110.162388"},{"key":"20001","doi-asserted-by":"crossref","unstructured":"Sekine Y, Togi S, Muromoto R. STAP-2 protein expression in B16F10 melanoma cells positively regulates protein levels of tyrosinase, which determines organs to infiltrate in the body. J Biol Chem. 2015; 290(28):17462-17473.","DOI":"10.1074\/jbc.M115.658575"},{"key":"20002","doi-asserted-by":"crossref","unstructured":"Fujita N, Oritani K, Ichii M. Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis. Eur J Immunol. 2014; 44(6):1791-1801.","DOI":"10.1002\/eji.201344239"},{"key":"20003","doi-asserted-by":"crossref","unstructured":"Arts RJ, Joosten LA, van der Meer JW, Netea MG. TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol. 2013; 93(2):209-215.","DOI":"10.1189\/jlb.0312145"},{"key":"20004","doi-asserted-by":"crossref","unstructured":"Ford JW, McVicar DW. TREM and TREMlike receptors in inflammation and disease. Curr Opin Immunol. 2009; 21(1):38-46.","DOI":"10.1016\/j.coi.2009.01.009"},{"key":"20005","doi-asserted-by":"crossref","unstructured":"Sharif O, Knapp S. From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. Immunobiology. 2008; 213(9-10):701-713.","DOI":"10.1016\/j.imbio.2008.07.008"},{"key":"20006","doi-asserted-by":"crossref","unstructured":"Li Q, Han D, Wang W. Toll-like receptor 4-mediated signaling regulates IL-7-driven proliferation and differentiation of B-cell precursors. Cell Mol Immunol. 2014; 11(2):132-140.","DOI":"10.1038\/cmi.2013.55"},{"key":"20007","doi-asserted-by":"crossref","unstructured":"Hayashi EA, Akira S, Nobrega A. Role of TLR in B cell development: signaling through TLR4 promotes B cell maturation and is inhibited by TLR2. J Immunol. 2005; 174(11):6639-6647.","DOI":"10.4049\/jimmunol.174.11.6639"},{"key":"20008","doi-asserted-by":"crossref","unstructured":"Sekine Y, Yamamoto C, Kakisaka M. Signal-transducing adaptor protein-2 modulates Fas-mediated T cell apoptosis by interacting with caspase-8. J Immunol. 2012; 188(12):6194-6204.","DOI":"10.4049\/jimmunol.1103467"},{"key":"20009","doi-asserted-by":"crossref","unstructured":"Sekine Y, Tsuji S, Ikeda O. Signal-transducing adaptor protein-2 regulates integrinmediated T cell adhesion through protein degradation of focal adhesion kinase. J Immunol. 2007; 179(4):2397-2407.","DOI":"10.4049\/jimmunol.179.4.2397"},{"key":"20010","doi-asserted-by":"crossref","unstructured":"Liao C, Hardison RC, Kennett MJ, Carlson BA, Paulson RF, Prabhu KS. Selenoproteins regulate stress erythroid progenitors and spleen microenvironment during stress erythropoiesis. Blood. 2018; 131(23):2568-2580.","DOI":"10.1182\/blood-2017-08-800607"},{"key":"20011","doi-asserted-by":"crossref","unstructured":"Peslak SA, Wenger J, Bemis JC. EPOmediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress. Blood. 2012; 120(12):2501-2511.","DOI":"10.1182\/blood-2011-11-394304"},{"key":"20012","doi-asserted-by":"crossref","unstructured":"Ueda Y, Yang K, Foster SJ, Kondo M, Kelsoe G. Inflammation controls B lymphopoiesis by regulating chemokine CXCL12 expression. J Exp Med. 2004; 199(1):47-58.","DOI":"10.1084\/jem.20031104"},{"key":"20013","doi-asserted-by":"crossref","unstructured":"Melamed D, Scott DW. Aging and neoteny in the B lineage. Blood. 2012; 120(20):4143-4149.","DOI":"10.1182\/blood-2012-07-444711"},{"key":"20014","doi-asserted-by":"crossref","unstructured":"Winkler IG, Bendall LJ, Forristal CE. Blymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2. Haematologica. 2013; 98(3):325-333.","DOI":"10.3324\/haematol.2012.069260"},{"key":"20015","doi-asserted-by":"crossref","unstructured":"Day RB, Bhattacharya D, Nagasawa T, Link DC. Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice. Blood. 2015; 125(20):3114-3117.","DOI":"10.1182\/blood-2015-02-629444"},{"key":"20016","doi-asserted-by":"crossref","unstructured":"Wang W, Org T, Montel-Hagen A. MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis. Nat Commun. 2016; 7:12376.","DOI":"10.1038\/ncomms12376"},{"key":"20017","doi-asserted-by":"crossref","unstructured":"Moreau JM, Berger A, Nelles ME. Inflammation rapidly reorganizes mouse bone marrow B cells and their environment in conjunction with early IgM responses. Blood. 2015; 126(10):1184-1192.","DOI":"10.1182\/blood-2015-03-635805"},{"key":"20018","doi-asserted-by":"crossref","unstructured":"Hua Z, Hou B. TLR signaling in B-cell development and activation. Cell Mol Immunol. 2013; 10(2):103-106.","DOI":"10.1038\/cmi.2012.61"},{"key":"20019","doi-asserted-by":"crossref","unstructured":"Matesanz-Isabel J, Sintes J, Llinas L, de Salort J, Lazaro A, Engel P. New B-cell CD molecules. Immunol Lett. 2011; 134(2):104-112.","DOI":"10.1016\/j.imlet.2010.09.019"}],"container-title":["Haematologica"],"original-title":[],"link":[{"URL":"https:\/\/haematologica.org\/article\/download\/9620\/70481","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/9620\/70482","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/haematologica.org\/article\/download\/9620\/70481","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T09:55:52Z","timestamp":1794045352000},"score":1,"resource":{"primary":{"URL":"https:\/\/haematologica.org\/article\/view\/9620"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,23]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2,1]]}},"URL":"https:\/\/doi.org\/10.3324\/haematol.2019.225573","relation":{},"ISSN":["1592-8721","0390-6078"],"issn-type":[{"value":"1592-8721","type":"electronic"},{"value":"0390-6078","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1,23]]}}}