Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases

Science. 2003 Oct 17;302(5644):445-9. doi: 10.1126/science.1088485.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Apoptosis
  • Bone Marrow Transplantation
  • Cell Adhesion
  • Cell Cycle
  • Cell Movement
  • Cell Size
  • Colony-Forming Units Assay
  • Cyclin D1 / metabolism
  • Fibronectins / metabolism
  • Hematopoiesis
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mitogen-Activated Protein Kinases / metabolism
  • Neutrophils / physiology*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Recombination, Genetic
  • Signal Transduction
  • Stem Cell Factor / pharmacology
  • Superoxides / metabolism
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Actins
  • Fibronectins
  • Proto-Oncogene Proteins
  • Stem Cell Factor
  • Superoxides
  • Cyclin D1
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • rac2 GTP-binding protein
  • rac GTP-Binding Proteins
  • rac1 GTP-Binding Protein