Stromal cell-derived factor 1-alpha (SDF)-induced human T cell chemotaxis becomes phosphoinositide 3-kinase (PI3K)-independent: role of PKC-theta.

Abstract:

:Stromal cell-derived factor 1alpha (SDF-1alpha) is the exclusive ligand for the chemokine receptor CXCR4. This receptor plays a pivotal role in immune responses, the pathogenesis of infection such as HIV, and cellular trafficking. However, the signaling mechanisms regulating SDF-driven T cell migration are not well defined. In this study, we determined the role of PI3K and protein kinase C- theta (PKC-theta) in SDF-induced human T cell migration in fresh versus cultured T cells. Purified human T cells (fresh vs. 48 h in media, unstimulated or activated by anti-CD3+anti-CD28) were used. Western blots showed that SDF induced phospho-(p)-Akt [threonine (Thr)308 and serine 473], a proxy for PI3K activity, in fresh cells and p-PKC-theta in 48 h unstimulated cells. LY294002 (PI3K inhibitor) reduced SDF-induced chemotaxis in fresh cells by 51%, whereas it minimally affected chemotaxis in 48 h unstimulated or activated cells. However, a specific PKC-theta inhibitor, pseudosubstrate for PKC-theta, reduced chemotaxis in 48 h unstimulated and stimulated T cells by 72% and 87%, respectively. Thus, chemotaxis becomes independent of PI3K signaling in human T cells cultured for 48 h. Under these conditions, PKC-theta is phosphorylated (Thr538) by SDF, and chemotaxis becomes largely PKC-theta-dependent.

journal_name

J Leukoc Biol

authors

Shahabi NA,McAllen K,Sharp BM

doi

10.1189/jlb.0607420

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

663-71

issue

3

eissn

0741-5400

issn

1938-3673

pii

jlb.0607420

journal_volume

83

pub_type

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