SEARCH:   Advanced

Blood, 1 March 2005, Vol. 105, No. 5, pp. 1923-1929. Prepublished online as a Blood First Edition Paper on November 12, 2004; DOI 10.1182/blood-2004-04-1450. This Article Full Text (PDF) All Versions of this Article: 2004-04-1450v1 105/5/1923    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Jelacic, T. Articles by Linnekin, D. Search for Related Content PubMed PubMed Citation Articles by Jelacic, T. Articles by Linnekin, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 16, 2004 Accepted October 27, 2004 PKC plays opposite roles in growth mediated by Wild-type Kit and an oncogenic Kit mutant Tanya Jelacic* and Diana Linnekin Basic Research Laboratory, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD, USA * Corresponding author; email: t_jelacic_obreiter{at}ncifcrf.gov. The Kit receptor tyrosine kinase is critical for normal hematopoiesis. Mutation of the aspartic acid residue encoded by codon 816 of human c-kit or codon 814 of the murine gene results in an oncogenic form of Kit. Here we investigate the role of PKC in responses mediated by wild-type murine Kit and the D814Y mutant in a murine mast cell-like line. PKC is activated after wild-type Kit binds SCF, is constitutively active in cells expressing the Kit catalytic domain mutant, and coprecipitates with both forms of Kit. Inhibition of PKChad opposite effects on growth mediated by wild-type and mutant Kit. Both rottlerin and a dominant negative PKC construct inhibited the growth of cells expressing mutant Kit, while SCF-induced growth of cells expressing wild-type Kit was not inhibited. Further, overexpression of PKC inhibited growth of cells expressing wild-type Kit and enhanced growth of cells expressing the Kit mutant. These data demonstrate that PKC contributes to factor-independent growth of cells expressing the D814Y mutant, but negatively regulates SCF-induced growth of cells expressing wild-type Kit. This is the first demonstration that PKC has different functions in cells expressing normal versus oncogenic forms of a receptor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Voisset, S. Lopez, P. Dubreuil, and P. De Sepulveda The tyrosine kinase FES is an essential effector of KITD816V proliferation signal Blood, October 1, 2007; 110(7): 2593 - 2599. [Abstract] [Full Text] [PDF] A. Tefferi Mutant Kit: thwarting the message down below Blood, March 15, 2005; 105(6): 2240 - 2241. [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020