• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Tatton, Louise
    Morley, Gary M
    Chopra, Rajesh
    Khwaja, Asim
    Affiliation
    Department of Haematology, Royal Free and University College Medical School, 98 Chenies Mews, London WC1E 6HX, United Kingdom.
    Issue Date
    2003-02-14
    
    Metadata
    Show full item record
    Abstract
    4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]- pyrimidine (PP1) was identified as an Src-selective tyrosine kinase inhibitor and has been used extensively to investigate signaling pathways involving Src kinases, including events downstream of the stem cell factor (SCF) receptor c-Kit. While investigating the role of Src kinases in SCF signaling, we found that PP1 completely abrogated the proliferation of M07e cells in response to SCF. PP1 inhibited SCF-induced c-Kit autophosphorylation in intact cells and blocked the activation of mitogen-activated protein kinase and Akt. In vitro kinase assays using immunoprecipitated c-Kit confirmed direct inhibition by PP1. SCF-induced c-Kit phosphorylation was also inhibited by the related inhibitor 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP2) and by STI571 but not by the Src inhibitor SU6656. PP1 inhibited the activity of mutant constitutively active forms of c-Kit (D814V and D814Y) found in mast cell disorders, and triggered apoptosis in the rat basophilic leukemia cell line RBL-2H3 that expresses mutant c-Kit. In addition, PP1 (and PP2) inhibited the in vitro kinase activity and autophosphorylation in whole cells of p210 Bcr-Abl. PP1 reduced the constitutive activation of signal transducer and activators of transcription 5 and mitogen-activated protein kinase and triggered apoptosis in FDCP1 cells expressing Bcr-Abl. These results have implications for the use of PP1 in investigating intracellular signaling and suggest that PP1 or related compounds may be useful in the treatment of malignant diseases associated with dysregulated c-Kit or Abl tyrosine kinase activity.
    Citation
    The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases. 2003, 278 (7):4847-53 J. Biol. Chem.
    Journal
    The Journal of Biological Chemistry
    URI
    http://hdl.handle.net/10541/79135
    DOI
    10.1074/jbc.M209321200
    PubMed ID
    12475982
    Type
    Article
    Language
    en
    ISSN
    0021-9258
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M209321200
    Scopus Count
    Collections
    All Christie Publications
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Lck associates with and is activated by Kit in a small cell lung cancer cell line: inhibition of SCF-mediated growth by the Src family kinase inhibitor PP1.
    • Authors: Krystal GW, DeBerry CS, Linnekin D, Litz J
    • Issue date: 1998 Oct 15
    • Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases.
    • Authors: Wisniewski D, Lambek CL, Liu C, Strife A, Veach DR, Nagar B, Young MA, Schindler T, Bornmann WG, Bertino JR, Kuriyan J, Clarkson B
    • Issue date: 2002 Aug 1
    • Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis.
    • Authors: Wilson MB, Schreiner SJ, Choi HJ, Kamens J, Smithgall TE
    • Issue date: 2002 Nov 21
    • Src family-selective tyrosine kinase inhibitor, PP1, inhibits both Fc epsilonRI- and Thy-1-mediated activation of rat basophilic leukemia cells.
    • Authors: Amoui M, Dráber P, Dráberová L
    • Issue date: 1997 Aug
    • Pyrazolo pyrimidine-type inhibitors of SRC family tyrosine kinases promote ovarian steroid-induced differentiation of human endometrial stromal cells in vitro.
    • Authors: Maruyama T, Yamamoto Y, Shimizu A, Masuda H, Sakai N, Sakurai R, Asada H, Yoshimura Y
    • Issue date: 2004 Jan
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.