共 54 条
Small molecule inhibitors of the Pyk2 and FAK kinases modulate chemoattractant-induced migration, adhesion and Akt activation in follicular and marginal zone B cells
被引:23
作者:
Tse, Kathy W. K.
[1
,2
]
Lin, Kevin B. L.
[1
,2
]
Dang-Lawson, May
[1
,2
]
Guzman-Perez, Angel
[3
]
Aspnes, Gary E.
[3
]
Buckbinder, Leonard
[3
]
Gold, Michael R.
[1
,2
]
机构:
[1] Univ British Columbia, Dept Microbiol & Immunol, Res Grp I3, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada
[2] Univ British Columbia, Dept Microbiol & Immunol, CELL Res Grp, Inst Life Sci, Vancouver, BC V6T 1Z3, Canada
[3] Pfizer Global Res & Dev, Groton, CT 06340 USA
基金:
加拿大健康研究院;
关键词:
B cells;
Marginal zone B cells;
Pyk2;
FAK;
CXCL13;
Sphingosine;
1-phosphate;
Cell migration;
Integrin-mediated adhesion;
Akt;
RICH TYROSINE KINASE-2;
COSTIMULATORY MOLECULES;
AUTOIMMUNE-DISEASES;
LYMPHOID ORGANS;
RAP GTPASES;
T-CELLS;
PHOSPHORYLATION;
MICE;
LYMPHOCYTES;
CHEMOKINE;
D O I:
10.1016/j.cellimm.2012.03.002
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
B-lymphocytes produce protective antibodies but also contribute to autoimmunity. In particular, marginal zone (MZ) B cells recognize both microbial components and self-antigens. B cell trafficking is critical for B cell activation and is controlled by chemoattactants such as CXCL13 and sphingosine 1-phosphate (SIP). The related tyrosine kinases focal adhesion kinase (FAK) and proline-rich tyrosine kinase (Pyk2) regulate cell migration and adhesion but their roles in B cells are not fully understood. Using a novel Pyk2-selective inhibitor described herein (PF-719), as well as a FAK-selective inhibitor, we show that both Pyk2 and FAK are important for CXCL13- and S1P-induced migration of B-2 cells and MZ B cells. In contrast, LFA-1-mediated adhesion required only Pyk2 whereas activation of the Akt pro-survival kinase required FAK but not Pyk2. Thus Pyk2 and FAK mediate critical processes in B cells and these inhibitors can be used to further elucidate their functions in B cells. (C) 2012 Elsevier Inc. All rights reserved.
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页码:47 / 54
页数:8
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