Discovery - University of Dundee - Online Publications

Library & Learning Centre

Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation

Standard

Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation. / Waugh, Caryll; Sinclair, Linda; Finlay, David; Bayascas, Jose R.; Cantrell, Doreen.

In: Molecular and Cellular Biology, Vol. 29, No. 21, 01.11.2009, p. 5952-5962.

Research output: Contribution to journalArticle

Harvard

Waugh, C, Sinclair, L, Finlay, D, Bayascas, JR & Cantrell, D 2009, 'Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation' Molecular and Cellular Biology, vol 29, no. 21, pp. 5952-5962.

APA

Waugh, C., Sinclair, L., Finlay, D., Bayascas, J. R., & Cantrell, D. (2009). Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation. Molecular and Cellular Biology, 29(21), 5952-5962doi: 10.1128/MCB.00585-09

Vancouver

Waugh C, Sinclair L, Finlay D, Bayascas JR, Cantrell D. Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation. Molecular and Cellular Biology. 2009 Nov 1;29(21):5952-5962.

Author

Waugh, Caryll; Sinclair, Linda; Finlay, David; Bayascas, Jose R.; Cantrell, Doreen / Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation.

In: Molecular and Cellular Biology, Vol. 29, No. 21, 01.11.2009, p. 5952-5962.

Research output: Contribution to journalArticle

Bibtex - Download

@article{dff5e84439614df9a5c45dcddb88a88d,
title = "Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation",
author = "Caryll Waugh and Linda Sinclair and David Finlay and Bayascas, {Jose R.} and Doreen Cantrell",
year = "2009",
volume = "29",
number = "21",
pages = "5952--5962",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Phosphoinositide (3,4,5)-triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates T-cell migration, not proliferation

A1 - Waugh,Caryll

A1 - Sinclair,Linda

A1 - Finlay,David

A1 - Bayascas,Jose R.

A1 - Cantrell,Doreen

AU - Waugh,Caryll

AU - Sinclair,Linda

AU - Finlay,David

AU - Bayascas,Jose R.

AU - Cantrell,Doreen

PY - 2009/11/1

Y1 - 2009/11/1

N2 - <p>The present study explored the consequences of phosphoinositide (3,4,5)-triphosphate [PI(3,4,5) P-3] binding to the pleckstrin homology (PH) domain of the serine/threonine kinase 3-phosphoinositide-dependent kinase 1 (PDK1). The salient finding is that PDK1 directly transduces the PI(3,4,5)P-3 signaling that determines T-cell trafficking programs but not T-cell growth and proliferation. The integrity of the PDK1 PH domain thus is not required for PDK1 catalytic activity or to support cell survival and the proliferation of thymic and peripheral T cells. However, a PDK1 mutant that cannot bind PI(3,4,5)P-3 cannot trigger the signals that terminate the expression of the transcription factor KLF2 in activated T cells and cannot switch the chemokine and adhesion receptor profile of naOve T cells to the profile of effector T cells. The PDK1 PH domain also is required for the maximal activation of Akt/protein kinase B (PKB) and for the maximal phosphorylation and inactivation of Foxo family transcription factors in T cells. PI(3,4,5)P-3 binding to PDK1 and the strength of PKB activity thus can dictate the nature of the T-cell response. Low levels of PKB activity can be sufficient for T-cell proliferation but insufficient to initiate the migratory program of effector T cells.</p>

AB - <p>The present study explored the consequences of phosphoinositide (3,4,5)-triphosphate [PI(3,4,5) P-3] binding to the pleckstrin homology (PH) domain of the serine/threonine kinase 3-phosphoinositide-dependent kinase 1 (PDK1). The salient finding is that PDK1 directly transduces the PI(3,4,5)P-3 signaling that determines T-cell trafficking programs but not T-cell growth and proliferation. The integrity of the PDK1 PH domain thus is not required for PDK1 catalytic activity or to support cell survival and the proliferation of thymic and peripheral T cells. However, a PDK1 mutant that cannot bind PI(3,4,5)P-3 cannot trigger the signals that terminate the expression of the transcription factor KLF2 in activated T cells and cannot switch the chemokine and adhesion receptor profile of naOve T cells to the profile of effector T cells. The PDK1 PH domain also is required for the maximal activation of Akt/protein kinase B (PKB) and for the maximal phosphorylation and inactivation of Foxo family transcription factors in T cells. PI(3,4,5)P-3 binding to PDK1 and the strength of PKB activity thus can dictate the nature of the T-cell response. Low levels of PKB activity can be sufficient for T-cell proliferation but insufficient to initiate the migratory program of effector T cells.</p>

KW - NF-Kappa-B

KW - Pleckstrin-homology-domain

KW - L-selectin

KW - Phosphatidylinositol 3-kinase

KW - Antigen receptor

KW - Immunological synapse

KW - Development requires

KW - Docking site

KW - PKC-theta

KW - In vivo

U2 - 10.1128/MCB.00585-09

DO - 10.1128/MCB.00585-09

M1 - Article

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 21

VL - 29

SP - 5952

EP - 5962

ER -

Documents

Library & Learning Centre

Contact | Accessibility | Policy