PMID- 31957000
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20210402
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 159
IP  - 4
DP  - 2020 Apr
TI  - Kit activates interleukin-4 receptor and effector signal transducer and activator 
      of transcription 6 independent of its cognate ligand in mouse mast cells.
PG  - 441-449
LID - 10.1111/imm.13174 [doi]
AB  - Signaling by Kit has been extensively studied in hematopoietic cells and is 
      essential for the survival, proliferation and maintenance of hematopoietic stem 
      and progenitor cells. In addition to the activation of intrinsic signaling 
      pathways, Kit has been shown to interact with lineage-restricted type I cytokine 
      receptors and produce cross signals, e.g. erythropoietin receptor, interleukin-7 
      receptor (IL-7R), IL-3R. Based on the earlier studies, we hypothesize that Kit 
      activate other type I cytokine receptors in a cell-specific manner and execute 
      cell-specific function. To investigate other Kit-activated receptors, we tested 
      Kit and IL-4R cross-receptor activation in murine bone-marrow-derived mast cells, 
      which express both Kit and IL-4R at the surface level. Kit upon activation by Kit 
      ligand (KL), activated IL-4Ralpha, gamma(C) , and signal transducer and activator of 
      transcription 6 independent of its cognate ligand IL-4. Though KL and IL-4 are 
      individually mitogenic, combinations of KL and IL-4 synergistically promoted mast 
      cell proliferation. Furthermore, inhibition of lipid raft formation by 
      methyl-beta-cyclodextrin resulted in loss of synergistic proliferation. Together the 
      data suggest IL-4R as a novel Kit-activated receptor. Such cross-receptor 
      activations are likely to be a universal mechanism of Kit signaling in 
      hematopoiesis.
CI  - (c) 2020 John Wiley & Sons Ltd.
FAU - Sethumadhavan, Aiswarya
AU  - Sethumadhavan A
AD  - Cell Signaling Laboratory, Department of Microbiology, School of Life Sciences, 
      Pondicherry University, Puducherry, India.
FAU - Mani, Maheswaran
AU  - Mani M
AUID- ORCID: 0000-0001-8056-8787
AD  - Cell Signaling Laboratory, Department of Microbiology, School of Life Sciences, 
      Pondicherry University, Puducherry, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200207
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Kit protein, mouse)
RN  - 0 (Receptors, Erythropoietin)
RN  - 0 (Receptors, Interleukin-3)
RN  - 0 (Receptors, Interleukin-4)
RN  - 0 (Receptors, Interleukin-7)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (Stem Cell Factor)
RN  - 0 (beta-Cyclodextrins)
RN  - 0 (interleukin-7 receptor, alpha chain)
RN  - 0 (methyl-beta-cyclodextrin)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/drug effects/immunology
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation
MH  - Hematopoiesis/drug effects/genetics/immunology
MH  - Interleukin-4/genetics/immunology/*pharmacology
MH  - Mast Cells/cytology/*drug effects/immunology
MH  - Membrane Microdomains/drug effects/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Primary Cell Culture
MH  - Proto-Oncogene Proteins c-kit/*genetics/immunology
MH  - Receptors, Erythropoietin/genetics/immunology
MH  - Receptors, Interleukin-3/genetics/immunology
MH  - Receptors, Interleukin-4/*genetics/immunology
MH  - Receptors, Interleukin-7/genetics/immunology
MH  - STAT6 Transcription Factor/*genetics/immunology
MH  - Signal Transduction
MH  - Stem Cell Factor/genetics/immunology/*pharmacology
MH  - beta-Cyclodextrins/pharmacology
PMC - PMC7077997
OTO - NOTNLM
OT  - Kit
OT  - Kit ligand
OT  - interleukin-4 receptor
OT  - lipid rafts
OT  - mast cells
COIS- The authors declare no commercial or financial conflict of interests.
EDAT- 2020/01/21 06:00
MHDA- 2020/07/28 06:00
PMCR- 2021/04/01
CRDT- 2020/01/21 06:00
PHST- 2019/07/27 00:00 [received]
PHST- 2019/12/01 00:00 [revised]
PHST- 2019/12/17 00:00 [accepted]
PHST- 2020/01/21 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
PHST- 2020/01/21 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - IMM13174 [pii]
AID - 10.1111/imm.13174 [doi]
PST - ppublish
SO  - Immunology. 2020 Apr;159(4):441-449. doi: 10.1111/imm.13174. Epub 2020 Feb 7.