Interleukin-2 induces β2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB)

被引:13
作者
Brockdorff, J [1 ]
Kanner, SB
Nielsen, M
Borregaard, N
Geisler, C
Svejgaard, A
Odum, N
机构
[1] Univ Copenhagen, Inst Med Microbiol & Immunol, DK-2200 Copenhagen N, Denmark
[2] Natl Univ Hosp, Dept Clin Immunol, Copenhagen, Denmark
[3] Natl Univ Hosp, Dept Hematol, Copenhagen, Denmark
[4] Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA
关键词
D O I
10.1073/pnas.95.12.6959
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
beta(2) integrin molecules are involved in a multitude of cellular events, including adhesion, migration, and cellular activation. Here, we studied the influence of beta(2) integrins on interleukin-2 (IL-2)-mediated signal transduction in human CD4(+) T cell lines obtained from healthy donors and a leukocyte adhesion deficiency (LAD) patient. We show that IL-2 induces tyrosine phosphorylation of a 125-kDa protein and homotypic adhesion in beta(2) integrin (CD18)-positive but not in beta(2)-integrin-negative T cells, EDTA, an inhibitor of integrin adhesion, blocks IL-2-induced tyrosine phosphorylation of the 125-kDa protein but not other proteins in beta(2)-integrin-positive T cells. Likewise, a beta(2) integrin (CD18) antibody selectively inhibits induction of the 125-kDa phosphotyrosine protein, whereas cytokine-mediated tyrosine phosphorylation of other proteins is largely unaffected. Immunoprecipitation experiments indicate that the IL-2-induced 125-kDa phosphotyrosine protein is the focal adhesion kinase-related protein B (fakB), Thus, IL-2 induces strong tyrosine phosphorylation of fakB in beta(2)-integrin-positive e but not in beta(2)-integrin-negative T cells, and CD18 mAb selectively blocks IL-2-induced fakB-tyrosine phosphorylation in Pz-integrin-positive T cells. In parallel experiments, IL-2 does not induce or augment tyrosine phosphorylation of p125(FAK). In conclusion, our data indicate that IL-2 induces beta(2)-integrin-dependent signal transduction events involving the tyrosine kinase substrate fakB.
引用
收藏
页码:6959 / 6964
页数:6
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