Signal transduction via the stem cell factor receptor/c-Kit

@article{Rnnstrand2004SignalTV,
  title={Signal transduction via the stem cell factor receptor/c-Kit},
  author={Lars R{\"o}nnstrand},
  journal={Cellular and Molecular Life Sciences CMLS},
  year={2004},
  volume={61},
  pages={2535-2548}
}
  • L. Rönnstrand
  • Published 1 October 2004
  • Biology, Chemistry
  • Cellular and Molecular Life Sciences CMLS
Abstract.Together with its ligand, stem cell factor, the receptor tyrosine kinase c-Kit is a key controlling receptor for a number of cell types, including hematopoietic stem cells, mast cells, melanocytes and germ cells. Gain-of-function mutations in c-Kit have been described in a number of human cancers, including testicular germinomas, acute myeloid leukemia and gastrointestinal stromal tumors.Stimulation of c-Kit by its ligand leads to dimerization of receptors, activation of its intrinsic… 
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409 Citations
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409 Citations

Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.

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The stem cell factor (SCF)/c-KIT signalling in testis and prostate cancer

TLDR
The present review provides an overview of the signalling pathways activated by SCF/c-KIT and discusses the potential application of c-K IT inhibitors for treatment of testicular and prostatic cancers.

Breakthroughs and Views Structure and regulation of Kit protein-tyrosine kinase—The stem cell factor receptor q

Signaling by stem cell factor and Kit, its receptor, play important roles in gametogenesis, hematopoiesis, mast cell development and function, and melanogenesis. Moreover, human and mouse embryonic…

Breakthroughs and Views Signaling by Kit protein-tyrosine kinase — The stem cell factor receptor q

TLDR
Stem cell factor exists as both a soluble and a membrane-bound glycoprotein while Kit is a receptor protein-tyrosine kinase that has the potential to participate in multiple signal transduction pathways as a result of interaction with several enzymes and adaptor proteins.

The stem cell factor receptor/c-Kit as a drug target in cancer.

TLDR
The current knowledge on the signal transduction molecules and pathways activated by c-Kit under normal conditions and in cancer cells, and the role of aberrant c- Kit signaling in cancer progression are highlighted.

Early myeloid cells expressing c-KIT isoforms differ in signal transduction, survival and chemotactic responses to Stem Cell Factor.

Emerging functions of c-kit and its ligand stem cell factor in dendritic cells

TLDR
This study shows that induction of c-kit expression and its signaling in DCs promotes Th2 and Th17 responses but not Th1 response, and reviews the differential expression pattern of SCF and c-Kit on various cell types and its avriation during development or pathology.

Role of c-KIT expression level and phosphatidylinositol 3-kinase activation in survival and proliferative responses of early myeloid cells.

c-Kit - The Novel Receptor: Physiological Roles, Downstream Signaling and Implications in Cancer

TLDR
The goal of this article is to provide a comprehensive review of the structure, function, signaling mechanisms of c-kit activation and its role in normal and pathological conditions.

Signaling Pathways Implicated in Hematopoietic Progenitor Cell Proliferation and Differentiation

TLDR
The data obtained indicated that committed hematopoietic progenitors express a certain level of constitutive signaling activity that participates in the regulation of normal steady-state hematoiesis and point to the importance of evaluating the impact of signal transduction inhibitors on normal bone marrow when used as potential therapeutic agents.
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References

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TLDR
SCF-induced PI-3'-kinase activation paralleled the increased SCF- induced mitogenicity after inhibition of PKC, and this report concluded that SCF's motility was affected by PKC's role as a modulatory role.

Stat1 associates with c-kit and is activated in response to stem cell factor.

TLDR
It is suggested that Stat1 is a component of the SCF signal-transduction pathway and that activated Stat1 binds the m67 oligonucleotide, a high-affinity SIE promoter sequence.

Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding

TLDR
It is demonstrated here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain, which may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.

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TLDR
Results indicate that Src family kinases play a role in ligand-induced trafficking of c-Kit, and this results indicate that SCF-responsive human hematopoietic cell line MO7e with the inhibitor of Srcfamily kinases PP1 is blocked.

Stat 1 associates with c-kit and is activated in response to stem cell factor

TLDR
Evidence that SCF activates the transcription factor Stat1 and phosphorylated c-kit co-immunoprecipitates with Stat1 within 1 min of SCF stimulation of the human cell line MO7e is presented.

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TLDR
Predictably, the lessons learned with Kit and Sl mice will be widely relevant to other pairs of ligands and receptors that control the function of different cell lineages and physiological processes.

c-kit ligand stimulates tyrosine phosphorylation of the c-Cbl protein in human hematopoietic cells.

TLDR
It is demonstrated that KL stimulates the rapid tyrosine phosphorylation of the proto-oncogene, c-Cbl, in two KL-responsive human hematopoietic cell lines, MO7e and TF-1, and it is suggested that c- Cbl is an important component in the KL signaling pathway in human heMatopOietic progenitor cells.

The Kit receptor promotes cell survival via activation of PI 3-kinase and subsequent Akt-mediated phosphorylation of Bad on Ser136

Activation of the MAP kinase pathway by c-Kit is PI-3 kinase dependent in hematopoietic progenitor/stem cell lines.

TLDR
The results suggest that a molecular signaling switch occurs during differentiation in the hematopoietic system whereby immature hematopolietic progenitor/stem cells use a PI-3 kinase-sensitive pathway in the activation of both Erk and PKB/Akt, which is then switched upon differentiation to the more commonly described PI- 3 Kinase-independent mitogen-activated protein (MAP) kinase pathway.

Phosphatidylinositol 3 kinase contributes to the transformation of hematopoietic cells by the D816V c-Kit mutant.

TLDR
It is indicated that constitutive activation of PI3K through direct recruitment by D816V c-Kit plays a role in factor-independent growth of MIHC and is critical for tumorigenicity.
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