PMID- 7692230
OWN - NLM
STAT- MEDLINE
DCOM- 19931026
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 13
IP  - 10
DP  - 1993 Oct
TI  - Mitogenic signalling and substrate specificity of the Flk2/Flt3 receptor tyrosine 
      kinase in fibroblasts and interleukin 3-dependent hematopoietic cells.
PG  - 6572-85
AB  - 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.
FAU - Dosil, M
AU  - Dosil M
AD  - Department of Molecular Biology, Princeton University, New Jersey 08544-1014.
FAU - Wang, S
AU  - Wang S
FAU - Lemischka, I R
AU  - Lemischka IR
LA  - eng
GR  - R01 CA45339/CA/NCI NIH HHS/United States
GR  - R01 DK42989/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Interleukin-3)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.67 (1-Phosphatidylinositol 4-Kinase)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (Flt3 protein, mouse)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
RN  - EC 3.1.4.- (Type C Phospholipases)
SB  - IM
MH  - 1-Phosphatidylinositol 4-Kinase
MH  - 3T3 Cells
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Division
MH  - Fibroblasts/cytology/*metabolism
MH  - GTPase-Activating Proteins
MH  - Hematopoietic Stem Cells/cytology/*metabolism
MH  - Humans
MH  - Interleukin-3/physiology
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins pp60(c-src)/metabolism
MH  - Receptor Protein-Tyrosine Kinases/*metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - *Signal Transduction
MH  - Substrate Specificity
MH  - Type C Phospholipases/metabolism
MH  - fms-Like Tyrosine Kinase 3
MH  - ras GTPase-Activating Proteins
PMC - PMC364716
EDAT- 1993/10/01 00:00
MHDA- 1993/10/01 00:01
PMCR- 1993/10/01
CRDT- 1993/10/01 00:00
PHST- 1993/10/01 00:00 [pubmed]
PHST- 1993/10/01 00:01 [medline]
PHST- 1993/10/01 00:00 [entrez]
PHST- 1993/10/01 00:00 [pmc-release]
AID - 10.1128/mcb.13.10.6572-6585.1993 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1993 Oct;13(10):6572-85. doi: 10.1128/mcb.13.10.6572-6585.1993.