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Science 7 June 1996:
Vol. 272. no. 5267, pp. 1492 - 1494
DOI: 10.1126/science.272.5267.1492
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Reports

Regulation of the Inositol 1,4,5-Trisphosphate Receptor by Tyrosine Phosphorylation

Thottala Jayaraman, Karol Ondrias, Elena Ondriasová, Andrew R. Marks *

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.

Laboratory for Molecular Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
* To whom correspondence should be addressed.


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