Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases.
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.
Gu
Yi
Y
Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Filippi
Marie-Dominique
MD
Cancelas
Jose A
JA
Siefring
Jamie E
JE
Williams
Emily P
EP
Jasti
Aparna C
AC
Harris
Chad E
CE
Lee
Andrew W
AW
Prabhakar
Rethinasamy
R
Atkinson
Simon J
SJ
Kwiatkowski
David J
DJ
Williams
David A
DA
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D048429:Cell Size; D003114:Colony-Forming Units Assay; D019938:Cyclin D1 / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011995:Recombination, Genetic; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
D000199:Actins; D019938:Cyclin D1; D005353:Fibronectins; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019089:Stem Cell Factor; D013481:Superoxides; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein