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Epo-R
The erythropoietin receptor (EpoR) is a protein that in humans is encoded by the ''EPOR'' gene. EpoR is a 52 kDa peptide with a single carbohydrate chain resulting in an approximately 56–57 kDa protein found on the surface of EPO responding cells. It is a member of the cytokine receptor family. EpoR pre-exists as dimers. These dimers were originally thought to be formed by extracellular domain interactions, however, it is now assumed that it is formed by interactions of the transmembrane domain and that the original structure of the extracellular interaction site was due to crystallisation conditions and does not depict the native conformation. Binding of a 30 kDa ligand erythropoietin (Epo), changes the receptor's conformational change, resulting in the autophosphorylation of Jak2 kinases that are pre-associated with the receptor (i.e., EpoR does not possess intrinsic kinase activity and depends on Jak2 activity). At present, the best-established function of EpoR ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Janus Kinase 2
Janus kinase 2 (commonly called JAK2) is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family (e.g. interferon receptors), the GM-CSF receptor family ( IL-3R, IL-5R and GM-CSF-R), the gp130 receptor family (e.g., IL-6R), and the single chain receptors (e.g. Epo-R, Tpo-R, GH-R, PRL-R). The distinguishing feature between janus kinase 2 and other JAK kinases is the lack of Src homology binding domains ( SH2/ SH3) and the presence of up to seven JAK homology domains (JH1-JH7). Nonetheless the terminal JH domains retain a high level of homology to tyrosine kinase domains. An interesting note is that only one of these carboxy-terminal JH domains retains full kinase function (JH1) while the other (JH2), previously thought to have no kinase functionality and accordingly termed a pseudokinase domain, has since been found to be catalytically active, albeit at only 10% ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metabolic reactions, DNA replication, Cell signaling, responding to stimuli, providing Cytoskeleton, structure to cells and Fibrous protein, organisms, and Intracellular transport, transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the Nucleic acid sequence, nucleotide sequence of their genes, and which usually results in protein folding into a specific Protein structure, 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called pep ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Erythroid Leukemia
Acute erythrocyte leukemia (AEL) is an extremely rare form of acute myeloid leukemia (less than 1% of AML cases) which is characterized by neoplastic proliferation of erythroid cells with features of maturation arrest (increased erythroblasts) and high prevalence of biallelic TP53 alterations. It is defined as type "M6" under the FAB classification. Signs and symptoms The most common symptoms of AEL are related to pancytopenia (a shortage of all types of blood cells), including fatigue, infections, and mucocutaneous bleeding. Almost half of people with AEL exhibit weight loss, fever and night sweats at the time of diagnosis. Almost all people with AEL are anemic, and 77% have a hemoglobin level under 10.0 g/dl. Signs of thrombocytopenia are found in about half of people with AEL. Causes The causes of AEL are unknown. Prior to a 2008 reclassification by the World Health Organization, cases that evolved from myelodysplastic syndromes, myeloproliferative neoplasms, chemotherapy for ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
STAT5A
Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the ''STAT5A'' gene. ''STAT5A'' orthologs have been identified in several placentals for which complete genome data are available. Structure STAT5a shares the same six functional domains as the other members of the STAT family. It contains 20 amino acids unique to its C-terminal domain and is 96% similar to its homolog, STAT5b. The six functional domains and their corresponding amino acid positions are as follows: * N-Terminal domain (aa1-144): stabilized interactions to form tetramers * Coiled-coil domain (aa145-330): interacts with chaperones and facilitates protein-protein interactions for transcriptional regulation * DNA binding domain (aa331-496): permits binding to consensus gamma-interferon activation sequence (GAS) * Linker domain (aa497-592): stabilizes DNA binding * Src Homology 2 domain (aa593-685): mediates receptor-specific recruitment and STAT dimerization via phosphor ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SOCS3
Suppressor of cytokine signaling 3 (SOCS3 or SOCS-3) is a protein that in humans is encoded by the ''SOCS3'' gene. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. SOCS3 is a conserved gene, found in across the animal kingdom, including ''Drosophila'', chickens, and crocodiles. Function The expression of SOCS3 gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. For signaling of IL-6, Epo, GCSF and Leptin, binding of SOCS3 to the respective cytokine receptor has been found to be crucial for the inhibitory function of SOCS3. Overexpression of SOCS3 inhibits insulin signaling in adipose tissue and the liver, but not in muscle. But deletion of SOCS3 in the skeletal muscle of mice protects against obesity-related insulin resistance. SOCS3 contributes to both leptin resistance a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SOCS2
Suppressor of cytokine signaling 2 is a protein that in humans is encoded by the ''SOCS2'' gene. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signalling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene can be induced by a subset of cytokines, including erythropoietin, GM-CSF, IL10 and interferon-gamma (IFN-gamma). The protein encoded by this gene is found to interact with the cytoplasmic domain of insulin-like growth factor 1 receptor (IGF1R), and thus is thought to be involved in the regulation of IGF1R mediated cell signaling. Knockout studies in mice also suggested a regulatory role of this gene in IGF-1 related growth control. Interactions SOCS2 has been shown to interact with insulin-like growth factor 1 receptor and erythropoietin receptor. Additionally, it acts as a substrate recognition subunit of a Cullin5 E3 ubiquitin ligas ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PTPN6
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' gene. Function The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog ( SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling, (e.g., the LYN-CD22-SHP-1 pathway). Multip ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PIK3R1
Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the ''PIK3R1'' gene. Function Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. The ''Pik3r1'' gene locus encodes the 85 kD regulatory subunit, as well as 55 and 50 kD regulatory subunits. It used to be thought that alternative splicing of this gene resulted in three transcript variants encoding different isoforms. In fact, it has since been shown that the 55 and 50kD subunits have their own promotors within the gene locus ''Pik3r1''. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Suppression specifically of the 85kD subunit in early murine embryoid body development results in a transient cell-cell adhe ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Grb2
Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/ cell communication. In humans, the GRB2 protein is encoded by the ''GRB2'' gene. The protein encoded by this gene binds receptors such as the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the ''sem-5'' gene of ''Caenorhabditis elegans'', which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. Function and expression Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types. It is thus n ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in the bone marrow. Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease. Erythropoietin is largely synthesized by fibroblast-like type-1 interstitial cells, located primarily in the deep renal cortex in close association with the peritubular capillaries and proximal convoluted tubule; it is also produced in perisinusoidal cells in the liver. Liver production predominates in the fetal and perinatal period; renal production predominates in adulthood. It is homologous with thrombopoietin. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CRKL
Crk-like protein is a protein that in humans is encoded by the CRKL gene. Function v-CRK avian sarcoma virus CT10-homolog-like contains one SH2 domain and two SH3 domains. CRKL has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase and plays a role in fibroblast transformation by BCR-ABL. In addition, CRKL has oncogenic potential. CrkL together with Crk participates in the Reelin signaling cascade downstream of DAB1. Interactions CRKL has been shown to interact with: * Abl gene, * BCAR1, * BCR gene, * CBLB, * CD117, * CD34, * Cbl gene, * Dock2, * EPOR, * GAB1, * GAB2, * INPP5D, * MAP4K1 Mitogen-activated protein kinase kinase kinase kinase 1 is a protein kinase that in humans is encoded by the ''MAP4K1'' gene. It is also known as HPK1 (Hematopoietic Progenitor Kinase 1). The protein has been shown to play a role in JNK activ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
