Abstract:
:Flk2/Flt3 is a recently identified receptor tyrosine kinase expressed in brain, placenta, testis, and primitive hematopoietic cells. The mitogenic signalling potential and biochemical properties of Flk2/Flt3 have been analyzed by using a chimeric receptor composed of the extracellular domain of the human colony-stimulating factor 1 receptor and the transmembrane and cytoplasmic domains of murine Flk2/Flt3. We demonstrate that colony-stimulating factor 1 stimulation of the Flk2/Flt3 kinase in transfected NIH 3T3 fibroblasts leads to a transformed phenotype and generates a full proliferative response in the absence of other growth factors. In transfected interleukin 3 (IL-3)-dependent Ba/F3 lymphoid cells, activation of the chimeric receptor can abrogate IL-3 requirement and sustain long-term proliferation. We show that phospholipase C-gamma 1, Ras GTPase-activating protein, the p85 subunit of phosphatidylinositol 3'-kinase, Shc, Grb2, Vav, Fyn, and Src are components of the Flk2/Flt3 signal transduction pathway. In addition, we demonstrate that phospholipase C-gamma 1, the p85 subunit of phosphatidylinositol 3'-kinase, Shc, Grb2, and Src family tyrosine kinases, but not Ras GTPase-activating protein, Vav, or Nck, physically associate with the Flk2/Flt3 cytoplasmic domain. Cell-type-specific differences in tyrosine phosphorylation of p85 and Shc are observed. A comparative analysis of the Flk2/Flt3 signal cascade with those of the endogenous platelet-derived growth factor and IL-3 receptors indicates that Flk2/Flt3 displays specific substrate preferences. Furthermore, tyrosine phosphorylation of p85 and Shc is similarly affected by totally different growth factors in the same cellular background.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Dosil M,Wang S,Lemischka IRdoi
10.1128/mcb.13.10.6572subject
Has Abstractpub_date
1993-10-01 00:00:00pages
6572-85issue
10eissn
0270-7306issn
1098-5549journal_volume
13pub_type
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journal_title:Molecular and cellular biology
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.15.2.1049
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/mcb.22.24.8398-8408.2002
更新日期:2002-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.2820
更新日期:1990-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.5.1130
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更新日期:1991-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.19.7.4711
更新日期:1999-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.8.5192
更新日期:1994-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.11.4.2040
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2002-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2011-02-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2008-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.6.3247
更新日期:1990-06-01 00:00:00