PMID- 9168474
OWN - NLM
STAT- MEDLINE
DCOM- 19970805
LR  - 20220409
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 8
IP  - 5
DP  - 1997 May
TI  - c-kit receptor signaling through its phosphatidylinositide-3'-kinase-binding site 
      and protein kinase C: role in mast cell enhancement of degranulation, adhesion, 
      and membrane ruffling.
PG  - 909-22
AB  - In bone marrow-derived mast cells (BMMCs), the Kit receptor tyrosine kinase 
      mediates diverse responses including proliferation, survival, chemotaxis, 
      migration, differentiation, and adhesion to extracellular matrix. In connective 
      tissue mast cells, a role for Kit in the secretion of inflammatory mediators has 
      been demonstrated as well. We recently demonstrated a role for 
      phosphatidylinositide-3' (PI 3)-kinase in Kit-ligand (KL)-induced adhesion of 
      BMMCs to fibronectin. Herein, we investigated the mechanism by which Kit mediates 
      enhancement of Fc epsilon RI-mediated degranulation, cytoskeletal rearrangements, 
      and adhesion in BMMCs. Wsh/Wsh BMMCs lacking endogenous Kit expression, were 
      transduced to express normal and mutant Kit receptors containing Tyr-->Phe 
      substitution at residues 719 and 821. Although the normal Kit receptor fully 
      restored KL-induced responses in Wsh/Wsh BMMCs, Kit gamma 719F, which fails to 
      bind and activate PI 3-kinase, failed to potentiate degranulation and is impaired 
      in mediating membrane ruffling and actin assembly. Inhibition of PI 3-kinase with 
      wortmannin or LY294002 also inhibited secretory enhancement and cytoskeletal 
      rearrangements mediated by Kit. In contrast, secretory enhancement and adhesion 
      stimulated directly through protein kinase C (PKC) do not require PI 3-kinase. 
      Calphostin C, an inhibitor of PKC, blocked Kit-mediated adhesion to fibronectin, 
      secretory enhancement, membrane ruffling, and filamentous actin assembly. 
      Although cytochalasin D inhibited Kit-mediated filamentous actin assembly and 
      membrane ruffling, secretory enhancement and adhesion to fibronectin were not 
      affected by this drug. Therefore, Kit-mediated cytoskeletal rearrangements that 
      are dependent on actin polymerization can be uncoupled from the Kit-mediated 
      secretory and adhesive responses. Our results implicate receptor-proximal PI 
      3-kinase activation and activation of a PKC isoform in Kit-mediated secretory 
      enhancement, adhesion, and cytoskeletal reorganization.
FAU - Vosseller, K
AU  - Vosseller K
AD  - Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, 
      USA.
FAU - Stella, G
AU  - Stella G
FAU - Yee, N S
AU  - Yee NS
FAU - Besmer, P
AU  - Besmer P
LA  - eng
GR  - R01-HL-51031/HL/NHLBI NIH HHS/United States
GR  - R31-CA-32926/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Actins)
RN  - 0 (Fibronectins)
RN  - 0 (Isoenzymes)
RN  - 0 (Phytohemagglutinins)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Binding Sites
MH  - Cell Adhesion/physiology
MH  - Cell Degranulation/physiology
MH  - Cell Membrane/ultrastructure
MH  - Fibronectins/metabolism
MH  - Isoenzymes/*metabolism
MH  - Mast Cells/cytology/metabolism/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phosphatidylinositol 3-Kinases
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Phytohemagglutinins
MH  - Protein Kinase C/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins c-kit/*metabolism
MH  - Ribosomal Protein S6 Kinases
MH  - Serotonin/metabolism
MH  - *Signal Transduction
MH  - Up-Regulation
PMC - PMC276137
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
AID - 10.1091/mbc.8.5.909 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1997 May;8(5):909-22. doi: 10.1091/mbc.8.5.909.