Foreskin keratinocyte (neonatal)
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Identification
- Summary
Foreskin keratinocyte (neonatal) is a treatment of skin cells used to accelerate wound closure and healing.
- Brand Names
- Gintuit
- Generic Name
- Foreskin keratinocyte (neonatal)
- DrugBank Accession Number
- DB10772
- Background
Skin, the largest organ of the human body, plays the main role in protecting the body from mechanical damage. It is composed of epidermal, dermal and hypodermal layers. The barrier function of the skin owed to its avascular epidermal layer, which is made mainly of keratinocytes. The keratinocytes form a stratified epithelium, with growing basal cells at the innermost layer and the keratinized, and mostly impermeable outer stratum corneum layer on the surface 3.
Foreskin keratinocytes are a form of skin cells that are cultured as a skin cell replacement for wounds, to accelerate wound closure and healing 1, 11.
The defining moment in skin culture was in 1975 when Rheinwald and Green successfully grew human keratinocytes on lethally irradiated murine fibroblasts. In 1981, O’Conner and his group utilized cultured autologous epithelium to coat burn defects for the first time. To construct a "living" alternative, a dermal substitute based on collagen I gel was created with mesenchymal cells such as fibroblasts. When an epidermal layer was added, this approach became known as "skin equivalent", "composite culture" or "organotypical culture" 4.
Foreskin keratinocytes are an important ingredient in several skin substitutes 11, used for various indications. Keratinocytes are derived from neonatal foreskins and used to create a drug called Apligraf, a mixture of Foreskin fibroblast (neonatal) and keratinocytes. A gel made of bovine collagen is used as the matrix for cell growth and differentiation. Apligraf has been useful in the treatment of venous leg ulcers and diabetic foot ulcers, by increasing rates of wound healing and decreasing the time required for closure of wounds 3.
Orcel, another skin substitute, is similar to Apligraf since it contains both fibroblasts and keratinocytes derived from neonatal foreskin, but in addition, utilizes a type I collagen sponge as its matrix. It is used for grafting onto partial-thickness wounds, where it offers a favorable matrix for host cell migration 3.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Cell transplant therapies
Other cell transplant therapies - Synonyms
- foreskin keratinocyte, neonatal
Pharmacology
- Indication
For chronic leg ulcers and diabetic foot 8.
Orcel is indicated for use with standard therapeutic compression for the treatment of non-infected partial and full-thickness skin ulcers due to venous insufficiency of greater than 1 month in duration and which have not effectively responded to conventional ulcer therapy. Orcel is also for use with standard diabetic foot ulcer care for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than 3 weeks in duration which have not effectively responded to conventional ulcer therapy, and which extend through the dermis but without tendon, muscle, capsule or bone involvement 10.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Wound of the oral cavity Combination Product in combination with: Bovine type I collagen (DB10771) •••••••••••• ••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Foreskin keratinocyte grafts lead to the re‐epithelialization of partial deep severe burns, thus allowing complete wound closure, and improves the condition of scars 5.
- Mechanism of action
Foreskin keratinocytes promote the proliferation of epithelial (skin) cells. Epidermal keratinocytes (skin cells) are very specialized epithelial cells designed for a very specific function, which is the separation of the organism from its outside environment. To provide this protection, the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments. The intermediate filaments are formed by keratin monomers and the cornified envelope is assembled from a protein called involucrin and several other proteins 13.
The following is a description of the mechanism of action of foreskin keratinocytes in various devices, while combined with other types of cells:
Orcel (epidermal keratinocytes and dermal fibroblasts) are cultured in two separate layers into a Type I bovine collagen sponge. Donor dermal fibroblasts are cultured on and within the porous sponge side of the collagen matrix while keratinocytes, from the same donor, are also cultured on the covered, non-porous side of the collagen matrix. Orcel acts as an absorbable matrix, providing a fertile environment for host cell migration and has been shown to contain the following cell-expressed cytokines with growth factors: FGF-1 (bFGF), NGF, GM-CSF, IL-1α, IL-1β, IL-6, HGF, KGF-1 (FGF- 7), M-CSF, PDGF-AB, TGF-α, TGF-β1, TGF-β2, and VEGF. DNA analysis performed on two Orcel treated donor site patient tissue samples demonstrated no trace of allogeneic cell DNA after 2-3 weeks post-treatment. Orcel is manufactured under aseptic conditions from human neonatal foreskin tissue 1.
Apligraf is supplied as a living, bi-layered skin substitute: the epidermal layer is formed by human keratinocytes and has a well-differentiated stratum corneum; the dermal layer is composed of human fibroblasts in a bovine Type I collagen lattice. While matrix proteins and cytokines found in human skin are present in Apligraf, Apligraf does not contain Langerhans cells, melanocytes, macrophages, lymphocytes, blood vessels or hair follicles. In a 10 patient venous leg ulcer study to determine the longevity of Apligraf cells, 2 of 8 patients evaluated at 4 weeks demonstrated Apligraf DNA. Neither of these patients showed Apligraf DNA at 8 weeks 12.
For dental applications, Gintuit (Allogeneic Cultured Keratinocytes and Fibroblasts in Bovine Collagen) is an allogeneic cellularized scaffold product indicated for topical application to a surgically created vascular wound bed in the treatment of mucogingival conditions in adults 9.
Target Actions Organism AFibroblast growth factor 1 agonistHumans AEpidermal growth factor receptor agonistHumans AGranulocyte-macrophage colony-stimulating factor receptor subunit alpha agonistHumans AInterleukin-1 beta agonistHumans AInterleukin-6 agonistHumans AInterferon gamma agonistHumans APlatelet-derived growth factor receptor alpha agonistHumans ATGF-beta receptor type-2 agonistHumans ATransforming growth factor beta-1 proprotein agonistHumans ATumor necrosis factor agonistHumans AVascular endothelial growth factor A, long form agonistHumans UFibroblast growth factor receptor 2 agonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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- Toxicity
Adverse events in a preclinical study of about 300 subjects were classified as mild, moderate, severe or life-threatening. In the venous leg ulcer study, 1 life-threatening infection and 3 severe infections reported in the Apligraf group occurred, and none in the control group. Of the 4 events, 2 severe infections were related to treatment: however one occurred one month after the last application of Apligraf and the other occurred following application on a pre-existing Pseudomonas infection 12.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Gintuit Foreskin keratinocyte (neonatal) + Bovine type I collagen + Foreskin fibroblast (neonatal) Cellular Sheet Topical Organogenesis 2012-03-15 Not applicable US
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- ZJO8CP3Q2A
- CAS number
- Not Available
References
- General References
- Pre-Clinical Demo Orcel [Link]
- Apligraf document, FDA [Link]
- Advances in Skin Substitutes—Potential of Tissue Engineered Skin for Facilitating Anti-Fibrotic Healing [Link]
- Skin Substitutes: A Brief Review of Types and Clinical Applications [Link]
- Foreskin‐isolated keratinocytes provide successful extemporaneous autologous paediatric skin grafts [Link]
- Allogeneic cultured keratinocytes/fibroblasts in bovine collagen (Rx) [Link]
- The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing [Link]
- Advancement of wound care from grafts to bioengineered smart skin substitutes [Link]
- Gintuit [Link]
- Orcel [Link]
- Advances in keratinocyte delivery in burn wound care [Link]
- Apligraf [Link]
- Molecular biology of keratinocyte differentiation. [Link]
- External Links
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data1, 2 Terminated Treatment Edentulous Alveolar Ridge 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Cellular sheet Topical - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as a potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrin ITGAV:ITGB3. Its binding to integrin, subsequent ternary complex formation with integrin and FGFR1, and the recruitment of PTPN11 to the complex are essential for FGF1 signaling. Induces the phosphorylation and activation of FGFR1, FRS2, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (PubMed:18441324, PubMed:20422052). Can induce angiogenesis (PubMed:23469107)
- Specific Function
- fibroblast growth factor receptor binding
- Gene Name
- FGF1
- Uniprot ID
- P05230
- Uniprot Name
- Fibroblast growth factor 1
- Molecular Weight
- 17459.58 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:10805725, PubMed:27153536, PubMed:2790960, PubMed:35538033). Known ligands include EGF, TGFA/TGF-alpha, AREG, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF (PubMed:12297049, PubMed:15611079, PubMed:17909029, PubMed:20837704, PubMed:27153536, PubMed:2790960, PubMed:7679104, PubMed:8144591, PubMed:9419975). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (PubMed:27153536). May also activate the NF-kappa-B signaling cascade (PubMed:11116146). Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling (PubMed:11602604). Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin (PubMed:11483589). Positively regulates cell migration via interaction with CCDC88A/GIV which retains EGFR at the cell membrane following ligand stimulation, promoting EGFR signaling which triggers cell migration (PubMed:20462955). Plays a role in enhancing learning and memory performance (By similarity). Plays a role in mammalian pain signaling (long-lasting hypersensitivity) (By similarity)
- Specific Function
- actin filament binding
- Gene Name
- EGFR
- Uniprot ID
- P00533
- Uniprot Name
- Epidermal growth factor receptor
- Molecular Weight
- 134276.185 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells
- Specific Function
- cytokine binding
- Gene Name
- CSF2RA
- Uniprot ID
- P15509
- Uniprot Name
- Granulocyte-macrophage colony-stimulating factor receptor subunit alpha
- Molecular Weight
- 46206.185 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Potent pro-inflammatory cytokine (PubMed:10653850, PubMed:12794819, PubMed:28331908, PubMed:3920526). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production (PubMed:3920526). Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850). Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 (PubMed:12794819). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33377178, PubMed:33883744). Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection (PubMed:28331908)
- Specific Function
- cytokine activity
- Gene Name
- IL1B
- Uniprot ID
- P01584
- Uniprot Name
- Interleukin-1 beta
- Molecular Weight
- 30747.7 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable)
- Specific Function
- cytokine activity
- Gene Name
- IL6
- Uniprot ID
- P05231
- Uniprot Name
- Interleukin-6
- Molecular Weight
- 23717.965 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity)
- Specific Function
- cytokine activity
- Gene Name
- IFNG
- Uniprot ID
- P01579
- Uniprot Name
- Interferon gamma
- Molecular Weight
- 19348.165 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor
- Specific Function
- ATP binding
- Gene Name
- PDGFRA
- Uniprot ID
- P16234
- Uniprot Name
- Platelet-derived growth factor receptor alpha
- Molecular Weight
- 122668.46 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and thus regulates a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and activation of TGFBR1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways
- Specific Function
- activin binding
- Gene Name
- TGFBR2
- Uniprot ID
- P37173
- Uniprot Name
- TGF-beta receptor type-2
- Molecular Weight
- 64567.1 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively
- Specific Function
- cytokine activity
- Gene Name
- TGFB1
- Uniprot ID
- P01137
- Uniprot Name
- Transforming growth factor beta-1 proprotein
- Molecular Weight
- 44324.645 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
- Specific Function
- cytokine activity
- Gene Name
- TNF
- Uniprot ID
- P01375
- Uniprot Name
- Tumor necrosis factor
- Molecular Weight
- 25644.15 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (PubMed:35455969). Involved in protecting cells from hypoxia-mediated cell death (By similarity)
- Specific Function
- chemoattractant activity
- Gene Name
- VEGFA
- Uniprot ID
- P15692
- Uniprot Name
- Vascular endothelial growth factor A, long form
- Molecular Weight
- 43596.94 Da
References
- Pre-Clinical Demo Orcel [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- General Function
- Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.
- Specific Function
- ATP binding
- Gene Name
- FGFR2
- Uniprot ID
- P21802
- Uniprot Name
- Fibroblast growth factor receptor 2
- Molecular Weight
- 92024.29 Da
References
- Pre-Clinical Demo Orcel [Link]
Drug created at December 01, 2015 20:04 / Updated at May 21, 2021 10:21