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69-640: 4U0I , 1PKG , 1T45 , 1T46 , 2E9W , 2EC8 , 2VIF , 3G0E , 3G0F , 4HVS , 4K94 , 4K9E , 4PGZ , 2IUH 3815 16590 ENSG00000157404 ENSMUSG00000005672 P10721 P05532 NM_000222 NM_001093772 NM_001122733 NM_021099 NP_000213 NP_001087241 NP_001116205 NP_066922 Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT , CD117 ( cluster of differentiation 117) or mast/stem cell growth factor receptor ( SCFR ). Multiple transcript variants encoding different isoforms have been found for this gene. KIT

138-407: A dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. After activation, the receptor is ubiquitinated to mark it for transport to a lysosome and eventual destruction. Signaling through KIT plays a role in cell survival, proliferation, and differentiation. For instance, KIT signaling

207-488: A KIT inhibitor, is determined by the mutation status of KIT: When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib . However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemias), the receptor is not inhibited by imatinib . In those cases other inhibitors such as dasatinib Avapritinib or nilotinib can be used. Researchers investigated

276-445: A clinical trial, scientists proposed that bone marrow transplantation could be used to treat HIV in conjunction with antiretroviral drugs; however, it was later found that HIV remained in the bodies of the test subjects. The stem cells are typically harvested directly from the red marrow in the iliac crest , often under general anesthesia . The procedure is minimally invasive and does not require stitches afterwards. Depending on

345-460: A group of enzymes that possess a catalytic domain with phosphotyrosine-specific phosphohydrolase activity. PTPs are capable of modifying the activity of receptor tyrosine kinases in both a positive and negative manner. PTPs can dephosphorylate the activated phosphorylated tyrosine residues on the RTKs which virtually leads to termination of the signal. Studies involving PTP1B, a widely known PTP involved in

414-560: A ligand-binding site, which binds extracellular ligands , e.g., a particular growth factor or hormone . The intracellular C terminal region displays the highest level of conservation and comprises catalytic domains responsible for the kinase activity of these receptors, which catalyses receptor autophosphorylation and tyrosine phosphorylation of RTK substrates. A kinase is a type of enzyme that transfers phosphate groups (see below) from high-energy donor molecules, such as ATP (see below) to specific target molecules ( substrates );

483-439: A newborn baby's bones exclusively contain hematopoietically active "red" marrow, and there is a progressive conversion towards "yellow" marrow with age. In adults, red marrow is found mainly in the central skeleton , such as the pelvis , sternum , cranium , ribs , vertebrae and scapulae , and variably found in the proximal epiphyseal ends of long bones such as the femur and humerus . In circumstances of chronic hypoxia,

552-427: A regulator of stemness in several cancers. Its expression has been linked to cancer stemness in ovarian cancer cells, colon cancer cells, non-small cell lung cancer cells, and prostate cancer cells. c-KIT has also been linked to the epithelial-mesenchymal transition (EMT), which is important for tumor aggressiveness and metastatic potential. Ectopic expression of c-KIT and EMT have been linked in denoid cystic carcinoma of

621-404: A signal through the plasma membrane. The phosphorylation of specific tyrosine residues within the activated receptor creates binding sites for Src homology 2 (SH2) domain- and phosphotyrosine binding (PTB) domain-containing proteins. Specific proteins containing these domains include Src and phospholipase C γ. Phosphorylation and activation of these two proteins on receptor binding lead to

690-452: A similar appearance. In GISTs, KIT staining is typically cytoplasmic , with stronger accentuation along the cell membranes . KIT antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas . KIT has been shown to interact with: Receptor tyrosine kinase The first RTKs to be discovered were the EGF and NGF receptors in

759-499: A similar pattern to subcutaneous fat. When "yellow" fatty marrow becomes replaced by tissue with more cellular composition, this change is apparent as decreased brightness on T1-weighted sequences. Both normal "red" marrow and pathologic marrow lesions (such as cancer) are darker than "yellow" marrow on T1-weight sequences, although can often be distinguished by comparison with the MR signal intensity of adjacent soft tissues. Normal "red" marrow

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828-473: A single hydrophobic transmembrane -spanning domain composed of 25 to 38 amino acids , an extracellular N terminal region, and an intracellular C terminal region. The extracellular N terminal region exhibits a variety of conserved elements including immunoglobulin (Ig)-like or epidermal growth factor (EGF)-like domains, fibronectin type III repeats, or cysteine-rich regions that are characteristic for each subfamily of RTKs; these domains contain primarily

897-449: A split tyrosine-kinase domain. VEGF-A binds to VEGFR-1 ( Flt-1 ) and VEGFR-2 ( KDR/Flk-1 ). VEGFR-2 appears to mediate almost all of the known cellular responses to VEGF. The function of VEGFR-1 is less well defined, although it is thought to modulate VEGFR-2 signaling. Another function of VEGFR-1 may be to act as a dummy/decoy receptor, sequestering VEGF from VEGFR-2 binding (this appears to be particularly important during vasculogenesis in

966-474: A subtype of testicular germ cell tumors , frequently have activating mutations in exon 17 of KIT. In addition, the gene encoding KIT is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon . Mutations of KIT have also been implicated in leukemia , a cancer of hematopoietic progenitors, melanoma , mast cell disease, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib (trade name Gleevec),

1035-449: A variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo , into osteoblasts , chondrocytes , myocytes , marrow adipocytes and beta-pancreatic islets cells . The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the membrane proteins , such as aquaporin and glycophorin , that are required to attach to and pass

1104-558: Is a center of a variety of immune activities: i) hematopoiesis, ii) osteogenesis, iii) immune responses, iv) distinction between self and non-self antigens, v) central immune regulatory function, vi) storage of memory cells, vii) immune surveillance of the central nervous system, viii) adaptation to energy crisis, ix) provision of mesenchymal stem cells for tissue repair. The bone marrow stroma contains mesenchymal stem cells (MSCs), which are also known as marrow stromal cells. These are multipotent stem cells that can differentiate into

1173-471: Is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases , such as multiple sclerosis and Alzheimer's disease . In mice, loss of signaling by any member of the ErbB family results in embryonic lethality with defects in organs including the lungs , skin , heart , and brain . Excessive ErbB signaling

1242-586: Is a nest for migratory memory T cells and a sanctuary for plasma cells. This has implications for adaptive immunity and vaccinology. Memory B and T cells persist in the parenchyma in dedicated survival niches organized by stromal cells. This memory can be maintained over long time periods in the form of quiescent cells or by repeated antigenic restimulation. Bone marrow protects and optimizes immunological memory during dietary restriction. In cancer patients, cancer-reactive memory T cells can arise in bone marrow spontaneously or after specific vaccination. Bone marrow

1311-409: Is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones . In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis ). It is composed of hematopoietic cells , marrow adipose tissue , and supportive stromal cells . In adult humans, bone marrow is primarily located in the ribs , vertebrae , sternum , and bones of

1380-505: Is also a marker for mouse prostate stem cells . In addition, mast cells , melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express KIT. In humans, expression of c-kit in helper-like innate lymphoid cells (ILCs) which lack the expression of CRTH2 (CD294) is used to mark the ILC3 population. CD117/c-KIT is expressed not only by bone marrow-derived stem cells, but also by those found in other adult organs, such as

1449-546: Is also being used for mobilization of hematopoietic progenitor cells. Direct KIT agonists are currently being developed as mobilization agents. Activating mutations in this gene are associated with gastrointestinal stromal tumors , testicular seminoma , mast cell disease, melanoma , acute myeloid leukemia , while inactivating mutations are associated with the genetic defect piebaldism . c-KIT plays an important role in regulating many mechanisms leading to tumor formation and progression of carcinomas. c-KIT has been proposed as

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1518-514: Is an anti-KIT, pyrrolobenzodiazepine (PBD)-containing antibody-drug conjugate which shows anti-tumor activity in vitro and in vivo against a range of tumor types. Antibodies to KIT are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for KIT, but negative for markers such as desmin and S-100 , which are positive in smooth muscle and neural tumors, which have

1587-439: Is associated with the development of a wide variety of types of solid tumor . ErbB-1 and ErbB-2 are found in many human cancers and their excessive signaling may be critical factors in the development and malignancy of these tumors . Fibroblast growth factors comprise the largest family of growth factor ligands at 23 members. The natural alternate splicing of four fibroblast growth factor receptor (FGFR) genes results in

1656-526: Is dynamic, as the mixture of cellular and non-cellular components (connective tissue) shifts with age and in response to systemic factors. In humans, marrow is colloquially characterized as "red" or "yellow" marrow ( Latin : medulla ossium rubra , Latin : medulla ossium flava , respectively) depending on the prevalence of hematopoietic cells vs fat cells . While the precise mechanisms underlying marrow regulation are not understood, compositional changes occur according to stereotypical patterns. For example,

1725-478: Is interrupted by a hydrophilic insert sequence of about 80 amino acids. The ligand stem cell factor binds via the second and third immunoglobulin domains. Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies , used to identify the cell type, stage of differentiation and activity of a cell. KIT is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in

1794-434: Is one of the main inducers of endothelial cell proliferation and permeability of blood vessels . Two RTKs bind to VEGF at the cell surface, VEGFR-1 ( Flt-1 ) and VEGFR-2 ( KDR/Flk-1 ). The VEGF receptors have an extracellular portion consisting of seven Ig -like domains so, like FGFRs, belong to the immunoglobulin superfamily. They also possess a single transmembrane spanning region and an intracellular portion containing

1863-441: Is relevant to bone marrow function, and also to diseases of the bone marrow and peripheral blood , such as leukemia and anemia. The normal myeloid-to-erythroid ratio is around 3:1; this ratio may increase in myelogenous leukemias , decrease in polycythemias , and reverse in cases of thalassemia . In a bone marrow transplant , hematopoietic stem cells are removed from a person and infused into another person ( allogenic ) or into

1932-408: Is required for melanocyte survival, and it is also involved in haematopoiesis and gametogenesis . Like other members of the receptor tyrosine kinase III family , KIT consists of an extracellular domain, a transmembrane domain, a juxtamembrane domain, and an intracellular tyrosine kinase domain. The extracellular domain is composed of five immunoglobulin-like domains, and the protein kinase domain

2001-567: Is required for the survival and proliferation of migrating myoblasts during myogenesis . A lack of c-met disrupts secondary myogenesis and—as in LBX1—prevents the formation of limb musculature. This local action of FGFs (Fibroblast Growth Factors) with their RTK receptors is classified as paracrine signalling . As RTK receptors phosphorylate multiple tyrosine residues, they can activate multiple signal transduction pathways. The ErbB protein family or epidermal growth factor receptor (EGFR) family

2070-523: Is typically equivalent or brighter than skeletal muscle or intervertebral disc on T1-weighted sequences. Fatty marrow change, the inverse of red marrow hyperplasia , can occur with normal aging, though it can also be seen with certain treatments such as radiation therapy . Diffuse marrow T1 hypointensity without contrast enhancement or cortical discontinuity suggests red marrow conversion or myelofibrosis . Falsely normal marrow on T1 can be seen with diffuse multiple myeloma or leukemic infiltration when

2139-402: The bone marrow . To be specific, hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of KIT. Common lymphoid progenitors (CLP) express low surface levels of KIT. KIT also identifies the earliest thymocyte progenitors in the thymus —early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It

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2208-458: The 1960s, but the classification of receptor tyrosine kinases was not developed until the 1970s. Approximately 20 different RTK classes have been identified. Most RTKs are single subunit receptors but some exist as multimeric complexes , e.g., the insulin receptor that forms disulfide linked dimers in the presence of hormone (insulin); moreover, ligand binding to the extracellular domain induces formation of receptor dimers. Each monomer has

2277-447: The FGFs themselves can also activate more than one receptor. This is not the case with FGF-7, however, which can activate only FGFR2b. A gene for a fifth FGFR protein, FGFR5, has also been identified. In contrast to FGFRs 1-4, it lacks a cytoplasmic tyrosine kinase domain, and one isoform, FGFR5γ, only contains the extracellular domains D1 and D2. Vascular endothelial growth factor (VEGF)

2346-588: The GDNF receptor-α (GFRα) protein family. Different members of the GFRα family (GFRα1-GFRα4) exhibit a specific binding activity for a specific GFLs. Upon GFL-GFRα complex formation, the complex then brings together two molecules of RET, triggering trans-autophosphorylation of specific tyrosine residues within the tyrosine kinase domain of each RET molecule. Phosphorylation of these tyrosines then initiates intracellular signal transduction processes. Ephrin receptors are

2415-457: The Src pathway. Herstatin is an autoinhibitor of the ErbB family, which binds to RTKs and blocks receptor dimerization and tyrosine phosphorylation. CHO cells transfected with herstatin resulted in reduced receptor oligomerization, clonal growth and receptor tyrosine phosphorylation in response to EGF. Activated RTKs can undergo endocytosis resulting in down regulation of the receptor and eventually

2484-467: The average molecular composition of soft tissues and thus provides information regarding the relative fat content of marrow. In adult humans, "yellow" fatty marrow is the dominant tissue in bones, particularly in the (peripheral) appendicular skeleton . Because fat molecules have a high T1-relaxivity , T1-weighted imaging sequences show "yellow" fatty marrow as bright (hyperintense). Furthermore, normal fatty marrow loses signal on fat-saturation sequences, in

2553-537: The blood at low levels. Mobilization is the process by which progenitors are made to migrate from the bone marrow into the bloodstream, thus increasing their numbers in the blood. Mobilization is used clinically as a source of hematopoietic stem cells for hematopoietic stem cell transplantation (HSCT). Signaling through KIT has been implicated in mobilization. At the current time, G-CSF is the main drug used for mobilization; it indirectly activates KIT. Plerixafor (an antagonist of CXCR4 - SDF1 ) in combination with G-CSF,

2622-405: The blood vessel endothelium . Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood. The red bone marrow is a key element of the lymphatic system , being one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells . The bone marrow and thymus constitute the primary lymphoid tissues involved in

2691-552: The blood. This procedure is similar to that used in blood or platelet donation. In adults, bone marrow may also be taken from the sternum , while the tibia is often used when taking samples from infants. In newborns, stem cells may be retrieved from the umbilical cord . Using quantitative polymerase chain reaction (qPCR) and next-generation sequencing (NGS) a maximum of five DNA viruses per individual have been identified. Included were several herpesviruses, hepatitis B virus, Merkel cell polyomavirus, and human papillomavirus 31. Given

2760-564: The body can convert yellow marrow back to red marrow to increase blood cell production. At the cellular level, the main functional component of bone marrow includes the progenitor cells which are destined to mature into blood and lymphoid cells. Human marrow produces approximately 500 billion blood cells per day. Marrow contains hematopoietic stem cells which give rise to the three classes of blood cells that are found in circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes). The stroma of

2829-407: The bone marrow includes all tissue not directly involved in the marrow's primary function of hematopoiesis . Stromal cells may be indirectly involved in hematopoiesis, providing a microenvironment that influences the function and differentiation of hematopoietic cells. For instance, they generate colony stimulating factors , which have a significant effect on hematopoiesis. Cell types that constitute

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2898-790: The bone marrow stroma include: That bone marrow is a priming site for T-cell responses to blood-borne antigens was first described in 2003. Mature circulating naïve T cells home to bone marrow sinuses after they have passed through arteries and arterioles. They transmigrate sinus endothelium and enter the parenchyma which contains dendritic cells (DCs). These have a capacity of antigen uptake, processing, and presentation. Cognate interactions between antigen-specific T cells and antigen-presenting DCs (APCs) in parenchyma lead to rapid T-APC cluster formation followed by T cell activation, T cell proliferation and T cell re-circulation to blood. These findings were corroborated and extended in 2013 by in situ two-photon dynamic imaging of mice skulls. Bone marrow

2967-407: The bone marrow, including certain forms of cancer such as leukemia . Several types of stem cells are related to bone marrow. Hematopoietic stem cells in the bone marrow can give rise to hematopoietic lineage cells, and mesenchymal stem cells , which can be isolated from the primary culture of bone marrow stroma, can give rise to bone, adipose , and cartilage tissue. The composition of marrow

3036-582: The borders of the bone marrow. People have used animal bone-marrow in cuisine worldwide for millennia, as in the famed Milanese Ossobuco . The normal bone marrow architecture can be damaged or displaced by aplastic anemia , malignancies such as multiple myeloma , or infections such as tuberculosis , leading to a decrease in the production of blood cells and blood platelets. The bone marrow can also be affected by various forms of leukemia , which attacks its hematologic progenitor cells. Furthermore, exposure to radiation or chemotherapy will kill many of

3105-450: The cellular elements of the blood, including platelets , red blood cells and white blood cells . While much information can be gleaned by testing the blood itself (drawn from a vein by phlebotomy ), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy. The ratio between myeloid series and erythroid cells

3174-400: The donor's health and reaction to the procedure, the actual harvesting can be an outpatient procedure , or can require 1–2 days of recovery in the hospital. Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood. An intravenous catheter is inserted into the donor's arm, and the stem cells are then filtered out of

3243-625: The dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting computational analysis. Their atomic investigation of mutant KIT receptor which emphasized on the EAL region provided a better insight into the understanding of the sunitinib resistance mechanism of the KIT receptor and could help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy. The preclinical agent, KTN0182A ,

3312-556: The embryo). A third receptor has been discovered (VEGFR-3); however, VEGF-A is not a ligand for this receptor. VEGFR-3 mediates lymphangiogenesis in response to VEGF-C and VEGF-D. The natural alternate splicing of the RET gene results in the production of 3 different isoforms of the protein RET. RET51, RET43, and RET9 contain 51, 43, and 9 amino acids in their C-terminal tail, respectively. The biological roles of isoforms RET51 and RET9 are

3381-447: The extracellular domain or the catalytic domain, thus inhibiting ligand binding, receptor oligomerization. Herceptin, a monoclonal antibody that is capable of binding to the extracellular domain of RTKs, has been used to treat HER2 overexpression in breast cancer. + Table adapted from "Cell signalling by receptor-tyrosine kinases," by Lemmon and Schlessinger's, 2010. Cell , 141 , p. 1117–1134. Bone marrow Bone marrow

3450-456: The ilium under general or local anesthesia . Bone marrow derived stem cells have a wide array of application in regenerative medicine. Medical imaging may provide a limited amount of information regarding bone marrow. Plain film x-rays pass through soft tissues such as marrow and do not provide visualization, although any changes in the structure of the associated bone may be detected. CT imaging has somewhat better capacity for assessing

3519-469: The initiation of signal transduction pathways. Other proteins that interact with the activated receptor act as adaptor proteins and have no intrinsic enzymatic activity of their own. These adaptor proteins link RTK activation to downstream signal transduction pathways, such as the MAP kinase signalling cascade . An example of a vital signal transduction pathway involves the tyrosine kinase receptor, c-met, which

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3588-575: The largest subfamily of RTKs. The DDRs are unique RTKs in that they bind to collagens rather than soluble growth factors. The receptor tyrosine kinase (RTK) pathway is carefully regulated by a variety of positive and negative feedback loops. Because RTKs coordinate a wide variety of cellular functions such as cell proliferation and differentiation, they must be regulated to prevent severe abnormalities in cellular functioning such as cancer and fibrosis. Protein Tyrosine Phosphatase (PTPs) are

3657-483: The marrow cavity of bones, although with low sensitivity and specificity. For example, normal fatty "yellow" marrow in adult long bones is of low density (-30 to -100 Hounsfield units), between subcutaneous fat and soft tissue. Tissue with increased cellular composition, such as normal "red" marrow or cancer cells within the medullary cavity will measure variably higher in density. MRI is more sensitive and specific for assessing bone composition. MRI enables assessment of

3726-442: The most well studied in-vivo , as these are the most common isoforms in which RET occurs. RET is the receptor for members of the glial cell line-derived neurotrophic factor (GDNF) family of extracellular signalling molecules or ligands (GFLs). In order to activate RET, first GFLs must form a complex with a glycosylphosphatidylinositol (GPI)-anchored co-receptor . The co-receptors themselves are classified as members of

3795-479: The new stem cells are introduced. Before radiation therapy or chemotherapy in cases of cancer , some of the patient's hematopoietic stem cells are sometimes harvested and later infused back when the therapy is finished to restore the immune system. Bone marrow stem cells can be induced to become neural cells to treat neurological illnesses, and can also potentially be used for the treatment of other illnesses, such as inflammatory bowel disease . In 2013, following

3864-685: The pelvis . Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow. Human marrow produces approximately 500 billion blood cells per day, which join the systemic circulation via permeable vasculature sinusoids within the medullary cavity . All types of hematopoietic cells, including both myeloid and lymphoid lineages , are created in bone marrow; however, lymphoid cells must migrate to other lymphoid organs (e.g. thymus ) in order to complete maturation. Bone marrow transplants can be conducted to treat severe diseases of

3933-409: The process is termed phosphorylation . The opposite, an enzyme that removes phosphate groups from targets, is known as a phosphatase . Kinase enzymes that specifically phosphorylate tyrosine amino acids are termed tyrosine kinases . When a growth factor binds to the extracellular domain of a RTK, its dimerization is triggered with other adjacent RTKs. Dimerization leads to a rapid activation of

4002-452: The production and early selection of lymphocytes. Furthermore, bone marrow performs a valve -like function to prevent the backflow of lymphatic fluid in the lymphatic system. Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance, erythrocytes , macrophages , and their precursors tend to gather around blood vessels , while granulocytes gather at

4071-416: The production of over 48 different isoforms of FGFR. These isoforms vary in their ligand binding properties and kinase domains; however, all share a common extracellular region composed of three immunoglobulin (Ig)-like domains (D1-D3), and thus belong to the immunoglobulin superfamily . Interactions with FGFs occur via FGFR domains D2 and D3. Each receptor can be activated by several FGFs. In many cases,

4140-433: The prostate, liver, and heart, suggesting that SCF/c-KIT signaling pathways may contribute to stemness in some organs. Additionally, c-KIT has been associated with numerous biological processes in other cell types. For example, c-KIT signaling, has been shown to regulate oogenesis, folliculogenesis, and spermatogenesis, playing important roles in female and male fertility. Hematopoietic progenitor cells are normally present in

4209-485: The protein's cytoplasmic kinase domains, the first substrate for these domains being the receptor itself. The activated receptor as a result then becomes autophosphorylated on multiple specific intracellular tyrosine residues . Through diverse means, extracellular ligand binding will typically cause or stabilize receptor dimerization. This allows a tyrosine in the cytoplasmic portion of each receptor monomer to be trans -phosphorylated by its partner receptor, propagating

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4278-410: The rapidly dividing cells of the bone marrow, and will therefore result in a depressed immune system . Many of the symptoms of radiation poisoning are due to damage sustained by the bone marrow cells. To diagnose diseases involving the bone marrow, a bone marrow aspiration is sometimes performed. This typically involves using a hollow needle to acquire a sample of red bone marrow from the crest of

4347-668: The reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for further studies. The earliest fossilised evidence of bone marrow was discovered in 2014 in Eusthenopteron , a lobe-finned fish which lived during the Devonian period approximately 370 million years ago. Scientists from Uppsala University and the European Synchrotron Radiation Facility used X-ray synchrotron microtomography to study

4416-414: The regulation of the cell cycle and cytokine receptor signaling, has shown to dephosphorylate the epidermal growth factor receptor and the insulin receptor. Some PTPs, on the other hand, are cell surface receptors that play a positive role in cell signaling proliferation. Cd45, a cell surface glycoprotein, plays a critical role in antigen-stimulated dephosphorylation of specific phosphotyrosines that inhibit

4485-500: The salivary gland, thymic carcinomas, ovarian cancer cells, and prostate cancer cells. Several lines of evidence suggest that SCF/c-KIT signaling plays an important role in the tumor microenvironment. For example, in mice high levels of c-KIT in mast cells as well as its presence in the tumor microenvironment promote angiogenesis, leading to increased tumor growth and metastasis. KIT is a proto-oncogene , meaning that overexpression or mutations of this protein can lead to cancer. Seminomas,

4554-434: The same person at a later time ( autologous ). If the donor and recipient are compatible, these infused cells will then travel to the bone marrow and initiate blood cell production. Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases, such as congenital defects, autoimmune diseases or malignancies. The patient's own marrow is first killed off with drugs or radiation , and then

4623-545: The signaling cascade. The molecular mechanism involves the engulfing of the RTK by a clathrin-mediated endocytosis, leading to intracellular degradation. RTKs have become an attractive target for drug therapy due to their implication in a variety of cellular abnormalities such as cancer, degenerative diseases and cardiovascular diseases. The United States Food and Drug Administration (FDA) has approved several anti-cancer drugs caused by activated RTKs. Drugs have been developed to target

4692-424: The water to fat ratio is not sufficiently altered, as may be seen with lower grade tumors or earlier in the disease process. Bone marrow examination is the pathologic analysis of samples of bone marrow obtained via biopsy and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, anemia , and pancytopenia . The bone marrow produces

4761-566: Was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit. KIT is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer . KIT is a receptor tyrosine kinase type III, which binds to stem cell factor , also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms

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