Publication Date:
2007-04-07
Description:
Pleckstrin homology (PH) domain-mediated protein recruitment to cellular membranes is of paramount importance for signal transduction. The recruitment of many PH domains is controlled through production and turnover of their membrane ligand, phosphatidylinositol 3,4,5-trisphosphate (PIP3). We show that phosphorylation of the second messenger inositol 1,4,5-trisphosphate (IP3) into inositol 1,3,4,5-tetrakisphosphate (IP4) establishes another mode of PH domain regulation through a soluble ligand. At physiological concentrations, IP4 promoted PH domain binding to PIP3. In primary mouse CD4+CD8+ thymocytes, this was required for full activation of the protein tyrosine kinase Itk after T cell receptor engagement. Our data suggest that IP4 establishes a feedback loop of phospholipase C-gamma1 activation through Itk that is essential for T cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yina H -- Grasis, Juris A -- Miller, Andrew T -- Xu, Ruo -- Soonthornvacharin, Stephen -- Andreotti, Amy H -- Tsoukas, Constantine D -- Cooke, Michael P -- Sauer, Karsten -- AR048848/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):886-9. Epub 2007 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17412921" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing/metabolism
;
*Amino Acid Motifs
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Animals
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Diglycerides/metabolism
;
Feedback, Physiological
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Inositol 1,4,5-Trisphosphate/metabolism
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Inositol Phosphates/*metabolism/pharmacology
;
Lymphopoiesis
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Membrane Proteins/metabolism
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Mice
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Mice, Inbred C57BL
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Models, Biological
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Organ Culture Techniques
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Phosphatidylinositol Phosphates/metabolism
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Phospholipase C gamma/metabolism
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Phosphoproteins/metabolism
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Phosphorylation
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Protein Structure, Tertiary
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Protein-Tyrosine Kinases/chemistry/*metabolism
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Receptors, Antigen, T-Cell/immunology
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Second Messenger Systems
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Signal Transduction
;
Solubility
;
T-Lymphocytes/cytology/immunology/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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