2p8v
From Proteopedia
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==Overview== | ==Overview== | ||
- | T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate | + | T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate in activating T cells, although understanding of how these pathways are themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are negative regulators of T cell activation. This is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin. Homer-NFAT binding was also antagonized by active serine-threonine kinase AKT, thereby enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT. This corresponded with changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice, which also developed autoimmune-like pathology. These results demonstrate a further means by which costimulatory signals are regulated to control self-reactivity. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bouyain, S.]] | [[Category: Bouyain, S.]] | ||
- | [[Category: Huang, G | + | [[Category: Huang, G N.]] |
[[Category: Leahy, D.]] | [[Category: Leahy, D.]] | ||
[[Category: Tu, J.]] | [[Category: Tu, J.]] | ||
- | [[Category: Worley, P | + | [[Category: Worley, P F.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: evh1 domain]] | [[Category: evh1 domain]] | ||
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[[Category: signaling protein]] | [[Category: signaling protein]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:27:10 2008'' |
Revision as of 16:27, 21 February 2008
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Crystal structure of human Homer3 EVH1 domain
Overview
T cell receptor (TCR) and costimulatory receptor (CD28) signals cooperate in activating T cells, although understanding of how these pathways are themselves regulated is incomplete. We found that Homer2 and Homer3, members of the Homer family of cytoplasmic scaffolding proteins, are negative regulators of T cell activation. This is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin. Homer-NFAT binding was also antagonized by active serine-threonine kinase AKT, thereby enhancing TCR signaling via calcineurin-dependent dephosphorylation of NFAT. This corresponded with changes in cytokine expression and an increase in effector-memory T cell populations in Homer-deficient mice, which also developed autoimmune-like pathology. These results demonstrate a further means by which costimulatory signals are regulated to control self-reactivity.
About this Structure
2P8V is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins., Huang GN, Huso DL, Bouyain S, Tu J, McCorkell KA, May MJ, Zhu Y, Lutz M, Collins S, Dehoff M, Kang S, Whartenby K, Powell J, Leahy D, Worley PF, Science. 2008 Jan 25;319(5862):476-81. PMID:18218901
Page seeded by OCA on Thu Feb 21 18:27:10 2008
Categories: Homo sapiens | Single protein | Bouyain, S. | Huang, G N. | Leahy, D. | Tu, J. | Worley, P F. | SO4 | Evh1 domain | Homer3 | Signaling protein