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Stromal cell‐derived factor 1‐α (SDF)‐induced human T cell chemotaxis becomes phosphoinositide 3‐kinase (PI3K)‐independent: role of PKC‐θ
Author(s) -
Shahabi Nahid A.,
McAllen K.,
Sharp Burt M.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0607420
Subject(s) - biology , chemotaxis , microbiology and biotechnology , phosphoinositide 3 kinase , stromal cell , protein kinase c , stem cell factor , pi3k/akt/mtor pathway , kinase , signal transduction , stem cell , cancer research , receptor , haematopoiesis , biochemistry
Stromal cell‐derived factor 1α (SDF‐1α) 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‐ θ (PKC‐θ) 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‐θ 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‐θ inhibitor, pseudosubstrate for PKC‐θ, 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‐θ is phosphorylated (Thr538) by SDF, and chemotaxis becomes largely PKC‐θ‐dependent.