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- Title
A function for tyrosine phosphorylation of type 1 inositol 1,4,5-trisphosphate receptor in lymphocyte activation.
- Authors
deSouza, Nikhil; Cui, Jie; Dura, Miroslav; McDonald, Thomas V.; Marks, Andrew R.
- Abstract
Sustained elevation of intracellular calcium by Ca[sup 2+] release-activated Ca[sup 2+] channels is required for lymphocyte activation. Sustained Ca[sup 2+] entry requires endoplasmic reticulum (ER) Ca[sup 2+] depletion and prolonged activation of inositol 1,4,5-trisphosphate receptor (IP[sub 3]R)/ Ca[sup 2+] release channels. However, a major isoform in lymphocyte ER, IP3R1, is inhibited by elevated levels of cytosolic Ca[sup 2+], and the mechanism that enables the prolonged activation of IP3R1 required for lymphocyte activation is unclear. We show that IP3R1 binds to the scaffolding protein linker of activated T cells and colocalizes with the T cell receptor during activation, resulting in persistent phosphorylation of IP[sub 3]R1 at Tyr353. This phosphorylation increases the sensitivity of the channel to activation by IP[sub 3] and renders the channel less sensitive to Ca[sup 2+]-induced inactivation. Expression of a mutant IP3R1-Y353F channel in lymphocytes causes defective Ca[sup 2+] signaling and decreased nuclear factor of activated T cells activation. Thus, tyrosine phosphorylation of IP3R1-Y353 may have an important function in maintaining elevated cytosolic Ca[sup 2+] levels during lymphocyte activation.
- Subjects
TYROSINE; INOSITOL phosphates; LYMPHOCYTE transformation; CALCIUM channels; ENDOPLASMIC reticulum; T cells
- Publication
Journal of Cell Biology, 2007, Vol 179, Issue 5, p923
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.200708200