Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils

被引：110

作者：

Filippi, MD

Harris, CE

Meller, J

Gu, Y

Zheng, Y

Williams, DA ^{[1
]}

机构：

[1] Univ Cincinnati, Coll Med, Div Expt Hematol, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Coll Med, Div Pediat Informat, Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA

来源：

NATURE IMMUNOLOGY | 2004年 / 5卷 / 07期

关键词：

D O I：

10.1038/ni1081

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Despite having a high degree of sequence similarity, the Rho guanosine triphosphatases Rac1 and Rac2 regulate distinct functions in neutrophils. Here we demonstrate that the unique Rac2 localization and functions in neutrophils are regulated by two separate C-terminal motifs, the hypervariable domain and aspartic acid 150, one of which has not previously been linked to the function of Rho GTPases. In addition, we show an unexpected dependence of Rac1 localization on Rac2 activity in these same cells, demonstrating a degree of crosstalk between two closely related Rho GTPases. Thus, we have defined specific sequences in Rac that specify subcellular localization and determine the specificity of Rac2 in neutrophil chemotaxis and superoxide generation.

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收藏

页码：744 / 751

页数：8

相关论文

共 37 条

[1] Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation [J].

Ambruso, DR ;

Knall, C ;

Abell, AN ;

Panepinto, J ;

Kurkchubasche, A ;

Thurman, G ;

Gonzalez-Aller, C ;

Hiester, A ;

deBoer, M ;

Harbeck, RJ ;

Oyer, R ;

Johnson, GL ;

Roos, D .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (09) :4654-4659

[2] H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway [J].

Apolloni, A ;

Prior, IA ;

Lindsay, M ;

Parton, RG ;

Hancock, JF .

MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (07) :2475-2487

[3] Characterization of Rac and Cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases [J].

Benard, V ;

Bohl, BP ;

Bokoch, GM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (19) :13198-13204

[4] Down-regulation of Rac activity during β2 integrin-mediated adhesion of human neutrophils [J].

Dib, K ;

Melander, F ;

Axelsson, L ;

Dagher, MC ;

Aspenström, P ;

Andersson, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (26) :24181-24188

[5]

DIDSBURY J, 1989, J BIOL CHEM, V264, P16378

[6] RAC GTPASE INTERACTS WITH GAPS AND TARGET PROTEINS THROUGH MULTIPLE EFFECTOR SITES [J].

DIEKMANN, D ;

NOBES, CD ;

BURBELO, PD ;

ABO, A ;

HALL, A .

EMBO JOURNAL, 1995, 14 (21) :5297-5305

[7] Palmitoylation and plasma membrane localization of Ras2p by a nonclassical trafficking pathway in Saccharomyces cerevisiae [J].

Dong, XW ;

Mitchell, DA ;

Lobo, S ;

Zhao, LH ;

Bartels, DJ ;

Deschenes, RJ .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (18) :6574-6584

[8] Spatial and temporal analysis of Rac activation during live neutrophil chemotaxis [J].

Gardiner, EM ;

Pestonjamasp, KN ;

Bohl, BP ;

Chamberlain, C ;

Hahn, KM ;

Bokoch, GM .

CURRENT BIOLOGY, 2002, 12 (23) :2029-2034

[9] Protein prenylation: from discovery to prospects for cancer treatment [J].

Gelb, MH ;

Scholten, JD ;

Sebolt-Leopold, JS .

CURRENT OPINION IN CHEMICAL BIOLOGY, 1998, 2 (01) :40-48

[10] Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions [J].

Glogauer, M ;

Marchal, CC ;

Zhu, F ;

Worku, A ;

Clausen, BE ;

Foerster, I ;

Marks, P ;

Downey, GP ;

Dinauer, M ;

Kwiatkowski, DJ .

JOURNAL OF IMMUNOLOGY, 2003, 170 (11) :5652-5657

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