Abstract
Tyrosine kinases indirectly raise intracellular calcium concentration ([Ca2+]i) by activating phospholipases that generate inositol 1,4,5-trisphosphate (IP3). IP3 activates the IP3 receptor (IP3R), an intracellular calcium release channel on the endoplasmic reticulum. T cell receptor stimulation triggered a physical association between the nonreceptor protein tyrosine kinase Fyn and the IP3R, which induced tyrosine phosphorylation of the IP3R. Fyn activated an IP3-gated calcium channel in vitro, and tyrosine phosphorylation of the IP3R during T cell activation was reduced in thymocytes from fyn-/- mice. Thus, activation of the IP3R by tyrosine phosphorylation may play a role in regulating [Ca2+]i.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Brain / metabolism
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Calcium / metabolism
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Calcium Channels / metabolism*
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism*
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Inositol 1,4,5-Trisphosphate / pharmacology
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Inositol 1,4,5-Trisphosphate Receptors
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Lipid Bilayers
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Lymphocyte Activation
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Mice
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Phosphorylation
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Phosphotyrosine / metabolism*
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins / pharmacology
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Proto-Oncogene Proteins c-fyn
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Receptors, Cytoplasmic and Nuclear / metabolism*
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tumor Cells, Cultured
Substances
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Calcium Channels
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ITPR1 protein, human
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Inositol 1,4,5-Trisphosphate Receptors
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Lipid Bilayers
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Proto-Oncogene Proteins
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Receptors, Cytoplasmic and Nuclear
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Phosphotyrosine
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Inositol 1,4,5-Trisphosphate
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Protein-Tyrosine Kinases
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FYN protein, human
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Fyn protein, mouse
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Proto-Oncogene Proteins c-fyn
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Calcium