CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors

Leonidas C. Platanias, Shahab Uddin, Edward Bruno, Mete Korkmaz, Sarfraz Ahmad, Yazan Alsayed, David Van Den Berg, Brian J. Druker, Amittha Wickrema, Ronald Hoffman

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Interferons are potent regulators of normal and malignant hematopoietic cell proliferation in vitro and in vivo, but the signaling mechanisms by which they exhibit their growth inhibitory effects are unknown. We have recently shown that CrkL is engaged in Type I IFN signaling, as shown by its rapid tyrosine phosphorylation during engagement of the Type I IFN receptor. In the present study, we provide evidence that the related CrkII protein is also rapidly phosphorylated on tyrosine during treatment of U-266 and Daudi cells with IFNα or IFNβ. We also show that both members of the Crk-family, CrkL and CrkII, are phosphorylated in an interferon-dependent manner in primary hematopoietic progenitors. Furthermore, inhibition of CrkL or CrkII protein expression by antisense oligonucleotides, reverses the inhibitory effects of IFNα or IFNγ on the proliferation of normal bone marrow progenitor cells (colony forming units-granulocytic/monocytic [CFU-GM] and burst-forming units-erythroid [BFU-E]). Thus, both CrkL and CrkII are engaged in a signaling pathway (s) that mediates interferon-regulated inhibition of hematopoietic cell proliferation.

Original languageEnglish (US)
Pages (from-to)1315-1321
Number of pages7
JournalExperimental hematology
Volume27
Issue number8
DOIs
StatePublished - Aug 1 1999

Keywords

  • Hematopoiesis
  • Interferons
  • Signal transduction

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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    Platanias, L. C., Uddin, S., Bruno, E., Korkmaz, M., Ahmad, S., Alsayed, Y., Van Den Berg, D., Druker, B. J., Wickrema, A., & Hoffman, R. (1999). CrkL and CrkII participate in the generation of the growth inhibitory effects of interferons on primary hematopoietic progenitors. Experimental hematology, 27(8), 1315-1321. https://doi.org/10.1016/S0301-472X(99)00060-0