Direct interaction between Kit and the interleukin-7 receptor

Jähn, Thomas; Sindhu, Simran; Gooch, Stacie; Seipel, Petra; Lavori, Philip W.; Leifheit, Erica C; Weinberg, Kenneth I.

doi:10.1182/blood-2005-12-028019

Cited by 23 publications

(25 citation statements)

References 52 publications

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“…Such mechanisms may potentially include yet unidentified, IL-7R␣ ligands or cross-activation of IL-7R␣ in Il7 Ϫ/Ϫ mice through other pathways, such as KIT, as recently suggested. 31 Although our findings do not support a key role of TSLP in IL-7-dependent or -independent steady state thymopoiesis, it remains possible that TSLP might be involved in T lymphopoiesis in conditions other than steady state.…”

Section: Discussioncontrasting

confidence: 49%

Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development

Jensen

Böiers

Kharazi

et al. 2008

Blood

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Although several cytokines have been demonstrated to be critical regulators of development of multiple blood cell lineages, it remains disputed to what degree they act through instructive or permissive mechanisms. Signaling through the FMS-like tyrosine kinase 3 (FLT3) receptor and the hematopoietin IL-7 receptor ␣ (IL-7R␣) has been demonstrated to be of critical importance for sustained thymopoiesis. Signaling triggered by IL-7 and thymic stromal lymphopoietin (TSLP) is dependent on IL-7R␣, and both ligands have been implicated in T-cell development. However, we demonstrate that, whereas thymopoiesis is abolished in adult mice doubly deficient in IL-7 and FLT3 ligand (FLT3L), TSLP does not play a key role in IL-7-independent or FLT3L-independent T lymphopoiesis. Furthermore, whereas previous studies implicated that the role of other cytokine tyrosine kinase receptors in T lymphopoiesis might not involve permissive actions, we demonstrate that ectopic expression of BCL2 is sufficient not only to partially correct the T-cell phenotype of Flt3l Ϫ/Ϫ mice but also to rescue the virtually complete loss of all discernable stages of early T lymphopoiesis in IntroductionGrowth factor dependent hematopoietic cell lines can on overexpression of the antiapoptotic regulator B-cell lymphoma-2 (BCL2) become independent of cytokines of the hematopoietin family. 1 In vivo studies demonstrating that defective thymopoiesis in interleukin-7 (IL-7)-and IL-7R␣-deficient (Il7 Ϫ/Ϫ and Il7r Ϫ/Ϫ ) mice can be rescued on overexpression of BCL2 2-4 or by deleting the proapoptotic regulator Bax, 5 further support the hypothesis that hematopoietin family cytokine receptors play a permissive role in thymopoiesis. Hematopoiesis is also regulated by a distinct family of cytokines acting through tyrosine kinase receptors, such as KIT oncogene (KIT) and FMS-like tyrosine kinase 3 (FLT3). 6 Notably, although KIT, like IL-7R␣, is critically involved in the regulation of thymopoiesis, BCL2 overexpression failed to rescue the impaired T lymphopoiesis in This implies that at least some members of this family of cytokine receptors and ligands, unlike the hematopoietin family, might not promote hematopoiesis through permissive actions.More recently, FLT3 ligand (FLT3L) has emerged as a key regulator of T lymphopoiesis, including of IL-7R␣-independent thymopoiesis, 8-12 but it has not been investigated to what degree FLT3 might act through permissive actions. Furthermore, as both IL-7 and thymic stromal lymphopoietin (TSLP) share the IL-7R␣, it is unclear to what degree the almost completely arrested T lymphopoiesis in adult Flt3l Ϫ/Ϫ Il7r Ϫ/Ϫ mice 8 reflects a role of FLT3L in conjunction with IL-7 and/or TSLP. TSLP also depends on and acts through a second IL-2R gamma chain (IL-2R␥)-like TSLP receptor (TSLPR) subunit 13 and has been shown to modulate immunologic responses by activating T cells through regulation of dendritic cells. 14 TSLP has also been implicated to play an important role in IL-7-independent B lymphopoiesis, as Il7r Ϫ/Ϫ mice have ...

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Section: Discussioncontrasting

confidence: 49%

Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development

Jensen

Böiers

Kharazi

et al. 2008

Blood

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“…It has been documented that c-Kit is able to crosstalk with many growth factor and cytokine receptors [26][27][28]81]. For example, erythropoietin and SCF have synergistic effects on erythropoiesis.…”

Section: C-kit and Insulin Receptor Crosstalk In Isletsmentioning

confidence: 99%

“…c-Kit signalling pathways are not simple linear reactions, but, rather, integrated inputs from different pathways that determine the biological consequences in different cellular contexts. For instance, c-Kit crosstalks with the erythropoietin receptor or interleukin receptors to recruit common downstream signalling molecules, creating a method for modulating diverse physiological responses [26][27][28][29].…”

Section: Scf and C-kit Signalling Pathwaysmentioning

confidence: 99%

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

et al. 2015

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The interactions between c-Kit and its ligand, stem cell factor (SCF), play an important role in haematopoiesis, pigmentation and gametogenesis. c-Kit is also found in the pancreas, and recent studies have revealed that c-Kit marks a subpopulation of highly proliferative pancreatic endocrine cells that may harbour islet precursors. c-Kit governs and maintains pancreatic endocrine cell maturation and function via multiple signalling pathways. In this review we address the importance of c-Kit signalling within the pancreas, including its profound role in islet morphogenesis, islet vascularisation, and beta cell survival and function. We also discuss the impact of c-Kit signalling in pancreatic disease and the use of c-Kit as a potential target for the development of cell-based and novel drug therapies in the treatment of diabetes.

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“…In support of such a possibility, evidence has recently been provided for such transactivation as an explanation for the more severe lymphoid phenotype in IL-7 receptor-than IL-7 ligand-deficient mice. 27 Resolving the conflicting results with regard to a potential role of FLT3 receptor and ligand in regulation of mouse HSCs has considerable implications for normal and leukemic hematopoiesis in man. Several studies have suggested that FLT3 is expressed on candidate normal human HSCs, [28][29][30] and greater than 30% of acute myeloid leukemias (AMLs) have activating mutations in the FLT3 receptor.…”

Section: Introductionmentioning

confidence: 99%

FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells

Buza‐Vidas

Cheng

Duarte

et al. 2009

Blood

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Direct interaction between Kit and the interleukin-7 receptor

Cited by 23 publications

References 52 publications

Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development

Permissive roles of hematopoietin and cytokine tyrosine kinase receptors in early T-cell development

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase

FLT3 receptor and ligand are dispensable for maintenance and posttransplantation expansion of mouse hematopoietic stem cells

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