The Erythropoietin Receptor: Biogenesis, Dimerization, and Intracellular Signal Transduction
- 1Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142; 2Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; 3The Walter and Eliza Hall Institute of Medical Research and the Cooperative Centre for Cellular Growth Factors, Parkville, Victoria, Australia
This extract was created in the absence of an abstract.
Excerpt
Erythropoietin (EPO), a 34-kD glycoprotein, is essential for the survival and proliferation of erythroid progenitor cells and their differentiation into erythrocytes. Like most receptors for hematopoietic growth factors, the EPO-R (D'Andrea et al. 1989) is a type I transmembrane protein and member of the cytokine receptor superfamily, which includes the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and interleukins IL-2, -3, -4, -5, -6, and -7. These receptors contain four conserved cysteines and a Trp-Ser-X-Trp-Ser motif in their extracellular domains (Cosman et al. 1990; Miyajima et al. 1992). The cytosolic domains of these receptors are dissimilar, and none contains intrinsic enzymatic activity.
Signaling through the EPO-R, like that of other cytokine receptors, is promoted by the activation of one or more protein-tyrosine kinases (PTKs) and is terminated by one or more protein-tyrosine phosphatases (PTPs) (Ihle et al. 1993; Darnell et al. 1994). Our work (Watowich et al....
