EPO-induced intracellular signaling pathways Erythropoietin and its receptor signaling through JAK2 activate multiple downstream signaling molecules including STAT5, PI3K/Akt, NF-κB, and MAPK. These factors may play an important role in inflammation and neuroprogression in the nervous system.
What receptor does EPO bind to?
The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the EPOR gene. EpoR is a 52kDa peptide with a single carbohydrate chain resulting in an approximately 56-57 kDa protein found on the surface of EPO responding cells….Erythropoietin receptor.
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What type of receptor is the EPO receptor?
-I cytokine receptor
The Epo-R is a classical Type-I cytokine receptor with an extracellular domain that interacts with the microenvironment, a transmembrane region that spans the phospholipid bilayer, and a cytoplasmic tail that contains eight tyrosine phosphorylation sites that serve as docking locations for signaling adapters.
Is EPO used in cancer treatment?
Erythropoietin (EPO) is a frequently prescribed drug for treatment of cancer-related and chemotherapy-induced anemia in cancer patients. Paradoxically, recent preclinical and clinical studies indicate that EPO could potentially accelerate tumor growth and jeopardize survival in cancer patients.
How does EPO signal?
Epo stimulates red blood cell production by binding and activating a high affinity receptor (EpoR) that is expressed predominantly on the surface of immature erythroid cells (Broudy et al., 1991).
How is EPO administered?
You have erythropoietin as an injection under the skin (subcutaneously). It is usually given into the thigh or tummy. A nurse can teach you, or a person caring for you, how to inject it. If you or a carer cannot give the injections, a district or practice nurse may do it for you.
Where is the EPO receptor?
erythroid progenitor cells
In the erythropoietic process, EPO induces homodimerization of the EPO receptor, which is located on the surface of erythroid progenitor cells.
What does EPO bind to?
EPO receptors
Secreted EPO (165 amino acids) binds to EPO receptors on the surface of bone marrow erythroid precursors, resulting in their rapid replication and maturation to functional red blood cells. This stimulation results in a rapid rise in erythrocyte counts and a consequent rise in blood oxygen.
Can you give Epogen to cancer patients?
Uses: Epogen is used to treat anemia, a lower than average number of red blood cells, that can be caused by chemotherapy. Epogen is given at the same time as chemotherapy. Epogen treatment stops when chemotherapy stops.
What is EPO oncology?
When is EPO released?
The hormone tells stem cells in the bone marrow to make more red blood cells. EPO is made by cells in the kidney. These cells release more EPO when blood oxygen level is low.
Where is EPO injected?
What is the role of EPO in cancer treatment?
Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitroand the identification of EPO receptors (EPORs) on neuronal cells. We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones.
How is the Epo-R receptor regulated?
Epo receptor (Epo-R) mutations. Epo-R signaling is regulated by the binding of the protein tyrosine phosphatase SHP-1 (or other JAK/STAT regulators) to the distal cytoplasmic region of Epo-R.
How does STAT5 bind to the activated EPO receptor?
In the case of the transcription factor STAT5, it binds to phosphorylated tyrosine 343 of the activated EPO receptor.
How does EPO bind to EpoR to inhibit apoptosis?
When EPO binds to EpoR, apoptosis is inhibited through an intracellular signaling cascade producing increased numbers of RBCs. EpoR-modulated gene transcription is regulated by SHP1 binding.
