Affiliations: Division of Hematology/Oncology, Children's Hospital
Boston, Dana-Farber Cancer Institute, and Harvard Stem Cell Institute, Harvard
Medical School, USA | Inha University School of Medicine, Korea
Note: [] Corresponding author: David A. Williams M.D., Chief of the
Division of Hematology/Oncology, Director of Translational Research for
Children's Hospital Boston, Leland Fikes Professor of Pediatrics, Harvard
Medical School, Children's Hospital Boston, 300 Longwood Ave, Karp 08125.3,
Boston MA 02115, USA. Tel.: +1 617 919 2697; Fax: +1 617 730 0868; E-mail:
[email protected]
Abstract: Rho GTPases are members of the Ras superfamily of GTPases that
regulate a wide variety of cellular functions. While Rho GTPase pathways have
been implicated in various pathological conditions in humans, to date coding
mutations in only the hematopoietic specific GTPase, RAC2, have been
found to cause a human disease, a severe phagocytic immunodeficiency
characterized by life-threatening infections in infancy. Interestingly, the
phenotype was predicted by a mouse knock-out of Rac2 and resembles
leukocyte adhesion deficiency (LAD). Here we review Rho GTPases with a specific
focus on Rac GTPases. In particular, we discuss a new understanding of the
unique and overlapping roles of Rac2 in blood cells that has developed since
the generation of mice deficient in Rac1, Rac2 and Rac3 proteins. We propose
that Rac2 mutations leading to disease be termed LAD type IV.
