Hematologic effects of inactivating the Ras processing enzyme Rce1
| Autor: | Abigail L. Aiyagari, Kevin Shannon, Stephen G. Young, Brigit R. Taylor, Vikas Aurora |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
Heterozygote Immunology Mutant Bone Marrow Cells Biology Biochemistry Leukocyte Count Mice Prenylation Endopeptidases medicine Extracellular Animals chemistry.chemical_classification Mice Knockout Kinase Hematopoietic Stem Cell Transplantation Granulocyte-Macrophage Colony-Stimulating Factor Cell Biology Hematology Adoptive Transfer Amino acid Cell biology Hematopoiesis Enzyme Activation Mice Inbred C57BL Haematopoiesis medicine.anatomical_structure chemistry Liver Mutation Bone marrow Mitogen-Activated Protein Kinases |
| Zdroj: | Blood. 101(6) |
| ISSN: | 0006-4971 |
| Popis: | Posttranslational processing of Ras proteins has attracted considerable interest as a potential target for anticancer drug discovery. Rcel encodes an endoprotease that facilitates membrane targeting of Ras and other prenylated proteins by releasing the carboxyl-terminal 3 amino acids (ie, the -AAX of the CAAX motif). Homozygous Rce1 mutant embryos (Ree - / - ) die late in gestation. To characterize the role of Rcel in hematopoiesis, we performed adoptive transfers and investigated cells from the recipients. Ree1 - / - fetal liver cells rescued lethally irradiated recipients and manifested normal long-term repopulating potential in competitive repopulation assays. The recipients of Rce1 - / - cells developed modest elevations in mature myeloid cells (neutrophils + monocytes), but remained well. Bone marrow cells from mice that received transplants of Rce1 - / - activated extracellular signal-related kinase (ERK) normally in response to granulocyte-macrophage colony-stimulating factor. These data suggest that pharmacologic inhibitors of Rcel will have minimal effects on normal hematopoietic cells. |
| Databáze: | OpenAIRE |
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