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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
41
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pubmed:dateCreated |
1997-11-13
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pubmed:abstractText |
As an attempt to analyze the roles of C-terminal Src kinase (Csk) in the high affinity IgE receptor (FcepsilonRI)-mediated signaling, we overexpressed Csk, a membrane-targeted form of Csk (mCsk), and a kinase-defective, membrane-targeted form of Csk (mCsk(-)) in rat basophil leukemia (RBL) 2H3 cells. Specific activity of Lyn at the basal state was decreased in Csk-expressing cells, and further decreased in mCsk-expressing cells. In mCsk(-)-expressing cells, basal specific activity of Lyn was increased, thereby indicating that mCsk(-) functioned as a dominant negative molecule. The onset of FcepsilonRI-mediated Lyn activation was delayed in Csk-expressing cells, and further delayed in mCsk-expressing cells. In mCsk(-)-expressing cells, Lyn activation was rapid and quite long lasting. These findings indicate (i) Csk negatively regulates rapid FcepsilonRI/Lyn coupling, and (ii) Csk activity is potentially required for its termination. The onsets of the series of events including tyrosyl phosphorylation of Syk, mitogen-activated protein (MAP) kinase activation, elevation of intracellular calcium concentration ([Ca2+]i), and histamine release were all stepwisely delayed in Csk-expressing cells and in mCsk-expressing cells. The durations of Syk phosphorylation and MAP kinase activation also closely correlated with those of Lyn activation, but [Ca2+]i elevation and histamine release followed different temporal patterns: the delayed responses in Csk-expressing cells and in mCsk-expressing cells led to sustained [Ca2+]i oscillation and histamine release, while the prompt responses in parent cells and mCsk(-)-expressing cells rapidly subsided. These findings provide further evidence that the initiations of the FcepsilonRI-mediated signals are upstreamly regulated by Src family protein tyrosine kinases and revealed that their terminations are regulated by Lyn-dependent (Syk and MAP kinase) and -independent ([Ca2+]i elevation and histamine release) mechanisms.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CSK tyrosine-protein kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgE,
http://linkedlifedata.com/resource/pubmed/chemical/lyn protein-tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25753-60
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:9325302-Amino Acid Sequence,
pubmed-meshheading:9325302-Animals,
pubmed-meshheading:9325302-Calcium,
pubmed-meshheading:9325302-Cell Line,
pubmed-meshheading:9325302-Enzyme Activation,
pubmed-meshheading:9325302-Kinetics,
pubmed-meshheading:9325302-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:9325302-Molecular Sequence Data,
pubmed-meshheading:9325302-Protein-Tyrosine Kinases,
pubmed-meshheading:9325302-Rats,
pubmed-meshheading:9325302-Receptors, IgE,
pubmed-meshheading:9325302-Signal Transduction,
pubmed-meshheading:9325302-src-Family Kinases
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pubmed:year |
1997
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pubmed:articleTitle |
Roles of C-terminal Src kinase in the initiation and the termination of the high affinity IgE receptor-mediated signaling.
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pubmed:affiliation |
Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113, Japan. honda-phy@h.u-tokyo.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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