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IL-7-induced phosphorylation of the adaptor Crk-like and other targets

  1. Author:
    Aiello, Francesca
    Guszczynski, Tad
    Li, Wenqing
    Jiang, Qiong
    Hodge, Deborah
    Massignan, Tania
    Di Lisio, Chiara
    Merchand, Anand
    Procopio, Antonio D
    Bonetto, Valentina
    Durum, Scott

  2. Author Address

    Cancer and Inflammation Program, CCR, NCI, NIH, Bldg 560, Frederick, MD 21702, USA. Electronic address: fbaiello@unich.it., Molecular Targets Laboratory, FCRDC, Bldg 560, Frederick, MD 21702, USA. Electronic address: Tad.guszczynski@mail.nih.gov., Cancer and Inflammation Program, CCR, NCI, NIH, Bldg 560, Frederick, MD 21702, USA. Electronic address: liwenq@mail.nih.gov., Cancer and Inflammation Program, CCR, NCI, NIH, Bldg 560, Frederick, MD 21702, USA. Electronic address: qiong.jiang@qiagen.com., Laboratory of Experimental Medicine, FCRDC, Bldg 560, Frederick, MD 21702, USA. Electronic address: hodged@mail.nih.gov., Dulbecco Telethon Institute, IRCCS-Istituto di Ricerche Farmacologiche M. Negri, via La Masa 19, 20156 Milano, Italy., Cancer and Inflammation Program, CCR, NCI, NIH, Bldg 560, Frederick, MD 21702, USA. Electronic address: chiara.dilisio@unich.it., Center for Cancer Research, NIH, Bethesda, MD 20892, USA. Electronic address: anand.merchant@nih.gov., Department of Clinical and Medical Sciences, Marche Polytechnic University, via Tronto 10, 60100 Ancona, Italy. Electronic address: a.d.procopio@univpm.it., Dulbecco Telethon Institute, IRCCS-Istituto di Ricerche Farmacologiche M. Negri, via La Masa 19, 20156 Milano, Italy. Electronic address: valentina.bonetto@marionegri.it., Cancer and Inflammation Program, CCR, NCI, NIH, Bldg 560, Frederick, MD 21702, USA. Electronic address: durums@mail.ncifcrf.gov.,
    1. Year: 2018
    2. Date: Mar 23
    3. Epub Date: 2018 03 23
  2. Journal: Cellular Signalling
    1. Pages: pii: S0898-6568(18)30073-1
  4. Type of Article: Article
  1. Abstract:

    IL-7 is required for T cell differentiation and mature T cell homeostasis and promotes pro-B cell proliferation and survival. Tyrosine phosphorylation plays a central role in IL-7 signaling. We identified by two-dimensional electrophoresis followed by anti-phosphotyrosine immunoblotting and mass spectrometry sixteen tyrosine phosphorylated proteins from the IL-7-dependent cell line D1. IL-7 stimulation induced the phosphorylation of the proteins STI1, ATIC and hnRNPH, involved in pathways related to survival, proliferation and gene expression, respectively, and increased the phosphorylation of CrkL, a member of a family of adaptors including the highly homologous Crk isoforms CrkII and CrkI, important in multiple signaling pathways. We observed an increased phosphorylation of CrkL in murine pro-B cells and in murine and human T cells. In addition, IL-7 increased the association of CrkL with the transcription factor Stat5, essential for IL-7 pro-survival activity. The selective tyrosine kinase inhibitor Imatinib. counteracted the IL-7 pro-survival effect in D1 cells and decreased CrkL phosphorylation. These data suggested that CrkL could play a pro-survival role in IL-7-mediated signaling. We observed that pro-B cells also expressed, in addition to CrkL, the Crk isoforms CrkII and CrkI and therefore utilized pro-B cells conditionally deficient in all three to evaluate the role of these proteins. The observation that the IL-7 pro-survival effect was reduced in Crk/CrkL conditionally-deficient pro-B cells further pointed to a pro-survival role of these adaptors. To further evaluate the role of these proteins, gene expression studies were performed in Crk/CrkL conditionally-deficient pro-B cells. IL-7 decreased the transcription of the receptor LAIR1, which inhibits B cell proliferation, in a Crk/CrkL-dependent manner, suggesting that the Crk family of proteins may promote pro-B cell proliferation. Our data contribute to the understanding of IL-7 signaling and suggest the involvement of Crk family proteins in pathways promoting survival and proliferation. Copyright © 2017. Published by Elsevier Inc.

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  2. DOI: 10.1016/j.cellsig.2018.03.008
  3. PMID: 29581031
  4. PII : S0898-6568(18)30073-1

Library Notes

  1. Fiscal Year: FY2017-2018
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