The Kit Receptor for the Stem Cell Factor: Genetic Lessons in Signal Transduction

1992 ◽  
pp. 311-324
Author(s):  
Sima Lev ◽  
Janna Blechmann ◽  
Allain Berrebi ◽  
David Givol ◽  
Yosef Yarden
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Stem Cell Factor ◽  
Kit Receptor

PANCREAS-TRANSDIFFERENTIATION INDUCED BY SIGNAL TRANSDUCTION SYSTEM OF STEM CELL FACTOR AND C-KIT RECEPTOR TYROSINE KINASE

Pancreas ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 493
Author(s):  
M. Satake ◽  
G. Eibl ◽  
K. Suzumura ◽  
T. Hirano ◽  
T. Okada ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Signal Transduction System ◽  
Kit Receptor

S1886 Pancreatic Transdifferentiation Induced By Signal Transduction System of c-Kit Receptor Tyrosine Kinase and Its Ligand Stem Cell Factor

2008 ◽  
Vol 134 (4) ◽  
pp. A-287
Author(s):  
Makoto Satake ◽  
Tetsuhiro Hamada ◽  
Guido Eibl ◽  
Kazuhiro Suzumura ◽  
Tadamichi Hirano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Stem Cell Factor ◽  
Signal Transduction System ◽  
Kit Receptor

Downregulation of c-kit (Stem Cell Factor Receptor) in Transformed Hematopoietic Precursor Cells by Stroma Cells

Blood ◽  
1999 ◽  
Vol 93 (2) ◽  
pp. 554-563 ◽  
Author(s):  
Christoph Heberlein ◽  
Jutta Friel ◽  
Christine Laker ◽  
Dorothee von Laer ◽  
Ulla Bergholz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Line ◽  
Stem Cell Factor ◽  
Progenitor Cell ◽  
Receptor Expression ◽  
General Mechanism ◽  
Ligand Interaction ◽  
Kit Ligand ◽  
Kit Receptor ◽  
Progenitor Cell Line

Abstract We show a dramatic downregulation of the stem cell factor (SCF) receptor in different hematopoietic cell lines by murine stroma. Growth of the human erythroid/macrophage progenitor cell line TF-1 is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). However, TF-1 cells clone and proliferate equally well on stroma. Independent stroma-dependent TF-1 clones (TF-1S) were generated on MS-5 stroma. Growth of TF-1S and TF-1 cells on stroma still requires interaction between c-kit (SCF receptor) and its ligand SCF, because antibodies against c-kit inhibit growth to less than 2%. Surprisingly, c-kit receptor expression (RNA and protein) was downregulated by 2 to 3 orders of magnitude in TF-1S and TF-1 cells grown on stroma. This stroma-dependent regulation of the kit receptor in TF-1 was also observed on exposure to kit ligand-negative stroma, thus indicating the need for heterologous receptor ligand interaction. Removal of stroma induced upregulation by 2 to 4 orders of magnitude. Downregulation and upregulation of c-kit expression could also be shown for the megakaryocytic progenitor cell line M-07e and was comparable to that of TF-1, indicating that stroma-dependent regulation of c-kit is a general mechanism. Downregulation may be an economic way to compensate for the increased sensitivity of the c-kit/ligand interaction on stroma. The stroma-dependent c-kit regulation most likely occurs at the transcriptional level, because mechanisms, such as splicing, attenuation, differential promoter usage, or mRNA stability, could be excluded.

scholarly journals Induction of Stem Cell Factor/c-Kit/Slug Signal Transduction in Multidrug-resistant Malignant Mesothelioma Cells

2004 ◽  
Vol 279 (45) ◽  
pp. 46706-46714 ◽  
Author(s):  
Alfonso Catalano ◽  
Sabrina Rodilossi ◽  
Maria Rita Rippo ◽  
Paola Caprari ◽  
Antonio Procopio
Keyword(s):  
Signal Transduction ◽  
Stem Cell ◽  
Malignant Mesothelioma ◽  
Stem Cell Factor ◽  
Multidrug Resistant ◽  
Factor C

scholarly journals Absence of abnormalities of c-kit or its ligand in two patients with Diamond-Blackfan anemia

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 25-28 ◽  
Author(s):  
JL Abkowitz ◽  
VC Broudy ◽  
LG Bennett ◽  
KM Zsebo ◽  
FH Martin
Keyword(s):  
Stem Cell ◽  
Clinical Features ◽  
Stem Cell Factor ◽  
Nucleotide Sequences ◽  
Diamond Blackfan Anemia ◽  
Coding Regions ◽  
Kit Receptor ◽  
Structural Abnormalities ◽  
Human Disorder ◽  
Normal Controls

As Diamond-Blackfan anemia shares clinical features with W and Steel defects in mice, we investigated the possibility that this human disorder might result from an abnormality of the c-kit receptor or its ligand, stem cell factor (SCF). For these studies, full nucleotide sequences for coding regions of c-kit and SCF were generated for two Diamond-Blackfan anemia patients and were normal. Similarly, the kds of SCF receptors on their marrow cells (31 pmol/L, 43 pmol/L) were comparable with those found in three normal controls (50 pmol/L, 55 pmol/L, 27 pmol/L). Serum SCF concentrations were 6.9 ng/mL in patient A, 14.6 ng/mL in patient B, who has been in hematologic remission since adolescence, and 2.7 ng/mL in the 3-year-old daughter of patient B, who also has Diamond-Blackfan anemia but is transfusion-dependent. It is possible that the SCF level in patient B increased with puberty, leading to her remission. These data provide evidence that Diamond- Blackfan anemia does not result from structural abnormalities of c-kit or SCF.

scholarly journals The rat c-kit ligand, stem cell factor, induces c-kit receptor-dependent mouse mast cell activation in vivo. Evidence that signaling through the c-kit receptor can induce expression of cellular function.

1992 ◽  
Vol 175 (1) ◽  
pp. 245-255 ◽  
Author(s):  
B K Wershil ◽  
M Tsai ◽  
E N Geissler ◽  
K M Zsebo ◽  
S J Galli
Keyword(s):  
Mast Cell ◽  
Stem Cell ◽  
Mast Cells ◽  
Stem Cell Factor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Tyrosine Kinase Receptor ◽  
Kit Ligand ◽  
Kit Receptor

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.

scholarly journals Stem cell factor influences the proliferation and erythroid differentiation of the MB-02 human erythroleukemia cell line by binding to a high-affinity c-kit receptor

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 436-444 ◽  
Author(s):  
VC Broudy ◽  
DA Morgan ◽  
N Lin ◽  
KM Zsebo ◽  
FW Jacobsen ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Stem Cell ◽  
Growth Factors ◽  
Cell Line ◽  
Stem Cell Factor ◽  
Erythroid Differentiation ◽  
Gm Csf ◽  
High Affinity ◽  
Kit Receptor ◽  
Erythroleukemia Cell

Abstract Stem cell factor (SCF) acts in synergy with other growth factors such as erythropoietin (Epo), granulocyte-macrophage colony-stimulating factor (GM-CSF), or interleukin-3 (IL-3), to stimulate the growth of primitive hematopoietic cells. Because of the prominent role of CSF in the maintenance of normal erythropoiesis in vivo, we examined the effects of SCF on the Epo-inducible human erythroleukemia cell line MB- 02, and characterized the c-kit receptor in these cells. MB-02 cells cultured in serum-containing media do not survive in the absence of exogenous growth factors, but the addition of SCF, Epo, or IL-3 as a single factor enhanced MB-02 survival. Furthermore, in the presence of Epo, SCF (5 to 25 ng/mL) enhanced MB-02 proliferation in a dose- dependent manner, and increased the relative and absolute number of benzidine-positive cells generated. SCF also enhanced cell proliferation in the presence of either IL-3 or low concentrations of GM-CSF. A neutralizing anti-c-kit receptor monoclonal antibody (SR-1) blocked binding of 125I-SCF to MB-02 cells by 98%, and the effect of SCF on MB-02 growth, c-kit receptor-binding parameters were quantitated by equilibrium-binding experiments with 125I-SCF. MB-02 cells display a single class of high-affinity (50 pmol/L) c-kit receptors, with approximately 8,000 receptors per cell. The molecular weight of the c- kit receptor was determined by affinity cross-linking 125I-SCF to MB-02 cells. 125I-SCF-c-kit receptor complexes of approximately 155,000 and approximately 310,000 daltons were found, likely representing the monomeric and dimeric forms of the c-kit receptor. The binding affinity and molecular weight of the c-kit receptor on MB-02 cells are similar to those of normal human marrow cells. These results suggest that SCF synergizes with Epo to influence not only the proliferation but the erythroid differentiation of MB-02 cells. Thus, the MB-02 cell line may be a useful model in which to investigate the molecular mechanisms of SCF action.

JAK2 is associated with the c-kit proto-oncogene product and is phosphorylated in response to stem cell factor

Blood ◽  
1996 ◽  
Vol 87 (9) ◽  
pp. 3688-3693 ◽  
Author(s):  
SR Weiler ◽  
S Mou ◽  
CS DeBerry ◽  
JR Keller ◽  
FW Ruscetti ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tyrosine Phosphorylation ◽  
Receptor Tyrosine Kinase ◽  
Antisense Oligonucleotides ◽  
Stem Cell Factor ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Kinase C ◽  
Kit Receptor ◽  
Normal Human

Stem cell factor (SCF) is a hematopoietic growth factor that interacts with the receptor tyrosine kinase, c-kit. We have found that SCF- stimulates rapid and transient tyrosine phosphorylation of JAK2 in human and murine cell lines, as well as in normal human progenitor cells. JAK2 and c-kit were associated in unstimulated cells with further recruitment of JAK2 to the c-kit receptor complex after SCF stimulation. Treatment of cells with JAK2 antisense oligonucleotides resulted in a 46% decrease in SCF-induced proliferation. These data demonstrate that SCF induces tyrosine phosphorylation of JAK2 and suggest that JAK2 is a component of the SCF signal transduction pathway.

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