CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase

K. E. Truitt, J. Shi, S. Gibson, L. G. Segal, Gordon Mills, J. B. Imboden

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28- mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.

Original languageEnglish (US)
Pages (from-to)4702-4710
Number of pages9
JournalJournal of Immunology
Volume155
Issue number10
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
T-Lymphocytes
Jurkat Cells
Interleukin-2
Ionomycin
Tyrosine
Cell Line
Mutation

ASJC Scopus subject areas

  • Immunology

Cite this

Truitt, K. E., Shi, J., Gibson, S., Segal, L. G., Mills, G., & Imboden, J. B. (1995). CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase. Journal of Immunology, 155(10), 4702-4710.

CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase. / Truitt, K. E.; Shi, J.; Gibson, S.; Segal, L. G.; Mills, Gordon; Imboden, J. B.

In: Journal of Immunology, Vol. 155, No. 10, 01.01.1995, p. 4702-4710.

Research output: Contribution to journalArticle

Truitt, KE, Shi, J, Gibson, S, Segal, LG, Mills, G & Imboden, JB 1995, 'CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase', Journal of Immunology, vol. 155, no. 10, pp. 4702-4710.
Truitt, K. E. ; Shi, J. ; Gibson, S. ; Segal, L. G. ; Mills, Gordon ; Imboden, J. B. / CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase. In: Journal of Immunology. 1995 ; Vol. 155, No. 10. pp. 4702-4710.
@article{75be2b5aa1c4430983bb7793acddbe49,
title = "CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase",
abstract = "CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28- mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.",
author = "Truitt, {K. E.} and J. Shi and S. Gibson and Segal, {L. G.} and Gordon Mills and Imboden, {J. B.}",
year = "1995",
month = "1",
day = "1",
language = "English (US)",
volume = "155",
pages = "4702--4710",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - CD28 delivers costimulatory signals independently of its association with phosphatidylinositol 3-kinase

AU - Truitt, K. E.

AU - Shi, J.

AU - Gibson, S.

AU - Segal, L. G.

AU - Mills, Gordon

AU - Imboden, J. B.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28- mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.

AB - CD28, a cell-surface molecule expressed by T cells, delivers costimulatory signals during the activation of T cells by Ag. Stimulation of CD28 induces its association with phosphatidylinositol 3'-kinase (PI3-K), raising the possibility that PI3-K plays a critical role in CD28 signaling. We find, however, that wortmannin, a potent inhibitor of PI3-K, does not block CD28- mediated costimulation of Jurkat (a human T cell line) or of murine CD4+ T cells. To address further the role of PI3-K in CD28-mediated signaling, we expressed mutant murine CD28 molecules in Jurkat cells. Mutation of Tyr 170 of murine CD28 to Phe abrogates the association of murine CD28 with PI3-K but does not affect the ability of murine CD28 to augment IL-2 production by Jurkat cells in response to the combination of ionomycin and PMA. Conversely, a mutant of murine CD28 that has a Tyr at position 170 but has Phe substitutions at the remaining three cytoplasmic tyrosines retains the ability to associate with PI3-K and has an impaired ability to deliver a costimulus that augments IL-2 production. CD28, therefore, can deliver costimulatory signals independently of its interaction with PI3-K, and association with PI3-K is insufficient to mediate the full effector function of CD28. Optimal signaling by CD28 requires the integrity of one or more of the carboxyl-terminal three Tyr residues.

UR - http://www.scopus.com/inward/record.url?scp=0028972549&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028972549&partnerID=8YFLogxK

M3 - Article

VL - 155

SP - 4702

EP - 4710

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -