Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes

Luo Sun; Hong Duk Youn; Christine Loh; Melissa Stolow; Weiwu He; Jun O. Liu

doi:10.1016/S1074-7613(00)80575-0

Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes

Luo Sun, Hong Duk Youn, Christine Loh, Melissa Stolow, Weiwu He, Jun O. Liu

Research output: Contribution to journal › Article › peer-review

197 Scopus citations

Abstract

Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin I that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross- talk between protein kinases and calcineurin.

Original language	English (US)
Pages (from-to)	703-711
Number of pages	9
Journal	Immunity
Volume	8
Issue number	6
DOIs	https://doi.org/10.1016/S1074-7613(00)80575-0
State	Published - Jun 1998
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

Access to Document

10.1016/S1074-7613(00)80575-0

Cite this

@article{46aeb73214b7434d9e3ae15ff53f0d4d,

title = "Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes",

abstract = "Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin I that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross- talk between protein kinases and calcineurin.",

author = "Luo Sun and Youn, {Hong Duk} and Christine Loh and Melissa Stolow and Weiwu He and Liu, {Jun O.}",

note = "Funding Information: We are grateful to Takahiro Nagase for the N-terminal human Cabin 1 cDNA clone (gene name KIAA 0330). We thank Steve Elledge for the mouse T cell cDNA library, Joe Heitman for the SMY4 yeast strain, Anjana Rao for an NF-ATp plasmid, Bin Su and Tieliang Deng for reporter plasmids, Jerry Crabtree for Tag Jurkat T cells, and Genhong Chen for advice on the yeast two-hybrid screen. We are grateful to Eric Griffith and Ben Turk for critically reading the manuscript. We thank Chris Armstrong for initiating yeast two-hybrid screens for cabins. This work was supported in part by the Chicago Community Trust, the Rita Allen Foundation, and the National Institutes of Health.",

year = "1998",

month = jun,

doi = "10.1016/S1074-7613(00)80575-0",

language = "English (US)",

volume = "8",

pages = "703--711",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

number = "6",

}

TY - JOUR

T1 - Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes

AU - Sun, Luo

AU - Youn, Hong Duk

AU - Loh, Christine

AU - Stolow, Melissa

AU - He, Weiwu

AU - Liu, Jun O.

N1 - Funding Information: We are grateful to Takahiro Nagase for the N-terminal human Cabin 1 cDNA clone (gene name KIAA 0330). We thank Steve Elledge for the mouse T cell cDNA library, Joe Heitman for the SMY4 yeast strain, Anjana Rao for an NF-ATp plasmid, Bin Su and Tieliang Deng for reporter plasmids, Jerry Crabtree for Tag Jurkat T cells, and Genhong Chen for advice on the yeast two-hybrid screen. We are grateful to Eric Griffith and Ben Turk for critically reading the manuscript. We thank Chris Armstrong for initiating yeast two-hybrid screens for cabins. This work was supported in part by the Chicago Community Trust, the Rita Allen Foundation, and the National Institutes of Health.

PY - 1998/6

Y1 - 1998/6

N2 - Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin I that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross- talk between protein kinases and calcineurin.

AB - Calcineurin plays a pivotal role in the T cell receptor (TCR)-mediated signal transduction pathway and serves as a common target for the immunosuppressants FK506 and cyclosporin A. We report the identification of a novel endogenous calcineurin binding protein named Cabin I that inhibits calcineurin-mediated signal transduction. The interaction between Cabin 1 and calcineurin is dependent on PKC activation. Overexpression of Cabin 1 or its N-terminal truncation mutants inhibits the transcriptional activation of calcineurin-responsive elements in the interleukin-2 promoter and blocks dephosphorylation of NF-AT upon T cell activation. These results suggest a negative regulatory role for Cabin 1 in calcineurin signaling and provide a possible mechanism of feedback inhibition of TCR signaling through cross- talk between protein kinases and calcineurin.

UR - http://www.scopus.com/inward/record.url?scp=0032101282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032101282&partnerID=8YFLogxK

U2 - 10.1016/S1074-7613(00)80575-0

DO - 10.1016/S1074-7613(00)80575-0

M3 - Article

C2 - 9655484

AN - SCOPUS:0032101282

SN - 1074-7613

VL - 8

SP - 703

EP - 711

JO - Immunity

JF - Immunity

IS - 6

ER -

Cabin 1, a negative regulator for calcineurin signaling in T lymphocytes

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this