Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-8-22
pubmed:abstractText
Protein-tyrosine kinases play crucial roles in mast cell activation through the high-affinity IgE receptor (FcepsilonRI). In this study, we have made the following observations on growth properties and FcepsilonRI-mediated signal transduction of primary cultured mast cells from Btk-, Lyn-, and Btk/Lyn-deficient mice. First, Lyn deficiency partially reversed the survival effect of Btk deficiency. Second, FcepsilonRI-induced degranulation and leukotriene release were almost abrogated in Btk/Lyn doubly deficient mast cells while singly deficient cells exhibited normal responses. Tyrosine phosphorylation of cellular proteins including phospholipases C-gamma1 and C-gamma2 was reduced in Btk/Lyn-deficient mast cells. Accordingly, FcepsilonRI-induced elevation of intracellular Ca2+ concentrations and activation of protein kinase Cs were blunted in the doubly deficient cells. Third, in contrast, Btk and Lyn demonstrated opposing roles in cytokine secretion and mitogen-activated protein kinase activation. Lyn-deficient cells exhibited enhanced secretion of TNF-alpha and IL-2 apparently through the prolonged activation of extracellular signal-related kinases and c-Jun N-terminal kinase. Potentially accounting for this phenomenon and robust degranulation in Lyn-deficient cells, the activities of protein kinase Calpha and protein kinase CbetaII, low at basal levels, were enhanced in these cells. Fourth, cytokine secretion was severely reduced and c-Jun N-terminal kinase activation was completely abrogated in Btk/Lyn-deficient mast cells. The data together demonstrate that Btk and Lyn are involved in mast cell signaling pathways in distinctly different ways, emphasizing that multiple signal outcomes must be evaluated to fully understand the functional interactions of individual signaling components.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1210-9
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:10903718-Animals, pubmed-meshheading:10903718-Bone Marrow Cells, pubmed-meshheading:10903718-Calcium Signaling, pubmed-meshheading:10903718-Cell Degranulation, pubmed-meshheading:10903718-Cell Differentiation, pubmed-meshheading:10903718-Cells, Cultured, pubmed-meshheading:10903718-Cytokines, pubmed-meshheading:10903718-Enzyme Activation, pubmed-meshheading:10903718-Histamine Release, pubmed-meshheading:10903718-Immunologic Deficiency Syndromes, pubmed-meshheading:10903718-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:10903718-Leukotrienes, pubmed-meshheading:10903718-Mast Cells, pubmed-meshheading:10903718-Mice, pubmed-meshheading:10903718-Mice, Inbred C57BL, pubmed-meshheading:10903718-Mice, Knockout, pubmed-meshheading:10903718-Mutation, pubmed-meshheading:10903718-Phosphorylation, pubmed-meshheading:10903718-Protein Kinase C, pubmed-meshheading:10903718-Protein-Tyrosine Kinases, pubmed-meshheading:10903718-Substrate Specificity, pubmed-meshheading:10903718-Transcriptional Activation, pubmed-meshheading:10903718-Tyrosine, pubmed-meshheading:10903718-src-Family Kinases
pubmed:year
2000
pubmed:articleTitle
Redundant and opposing functions of two tyrosine kinases, Btk and Lyn, in mast cell activation.
pubmed:affiliation
Division of Allergy, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't