Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases

被引：401

作者：

Gu, Y

Filippi, MD

Cancelas, JA

Siefring, JE

Williams, EP

Jasti, AC

Harris, CE

Lee, AW

Prabhakar, R

Atkinson, SJ

Kwiatkowski, DJ

Williams, DA ^{[1
]}

机构：

[1] Cincinnati Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA

[2] Univ Cincinnati, Coll Med, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA

[3] Indiana Univ, Dept Med, Indianapolis, IN 46202 USA

[4] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

来源：

SCIENCE | 2003年 / 302卷 / 5644期

关键词：

D O I：

10.1126/science.1088485

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：

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1(-/-) but not Rac2(-/-) HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.

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收藏

页码：445 / 449

页数：5

相关论文

共 25 条

[1] ACTIVATION OF THE NADPH OXIDASE INVOLVES THE SMALL GTP-BINDING PROTEIN P21RAC1 [J].

ABO, A ;

PICK, E ;

HALL, A ;

TOTTY, N ;

TEAHAN, CG ;

SEGAL, AW .

NATURE, 1991, 353 (6345) :668-670

[2] The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes [J].

Croker, BA ;

Tarlinton, DM ;

Cluse, LA ;

Tuxen, AJ ;

Light, A ;

Yang, FC ;

Williams, DA ;

Roberts, AW .

JOURNAL OF IMMUNOLOGY, 2002, 168 (07) :3376-3386

[3] CONDITIONS CONTROLLING PROLIFERATION OF HEMATOPOIETIC STEM-CELLS INVITRO [J].

DEXTER, TM ;

ALLEN, TD ;

LAJTHA, LG .

JOURNAL OF CELLULAR PHYSIOLOGY, 1977, 91 (03) :335-344

[4] Rho GTPases in cell biology [J].

Etienne-Manneville, S ;

Hall, A .

NATURE, 2002, 420 (6916) :629-635

[5] 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

[6] DELETION OF A DNA-POLYMERASE-BETA GENE SEGMENT IN T-CELLS USING CELL-TYPE-SPECIFIC GENE TARGETING [J].

GU, H ;

MARTH, JD ;

ORBAN, PC ;

MOSSMANN, H ;

RAJEWSKY, K .

SCIENCE, 1994, 265 (5168) :103-106

[7] Rac2, a hematopoiesis-specific Rho GTPase, specifically regulates mast cell protease gene expression in bone marrow-derived mast cells [J].

Gu, Y ;

Byrne, MC ;

Paranavitana, NC ;

Aronow, B ;

Siefring, JE ;

D'Souza, M ;

Horton, HF ;

Quilliam, LA ;

Williams, DA .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (21) :7645-7657

[8] Characterization of RAC3, a novel member of the Rho family [J].

Haataja, L ;

Groffen, J ;

Heisterkamp, N .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (33) :20384-20388

[9] Rho GTPases and the actin cytoskeleton [J].

Hall, A .

SCIENCE, 1998, 279 (5350) :509-514

[10] REGULATION OF PHAGOCYTE OXYGEN RADICAL PRODUCTION BY THE GTP-BINDING PROTEIN RAC-2 [J].

KNAUS, UG ;

HEYWORTH, PG ;

EVANS, T ;

CURNUTTE, JT ;

BOKOCH, GM .

SCIENCE, 1991, 254 (5037) :1512-1515