Search results for KDR

Showing 15 results out of 16

×

Species

Types

Compartments

Reaction types

Search properties

Species

Types

Compartments

Reaction types

Search properties

Protein (4 results from a total of 4)

Identifier: R-HSA-195382
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: KDR: P35968
Identifier: R-HSA-4420103
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: KDR: P35968
Identifier: R-HSA-9673613
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: KDR: P35968
Identifier: R-HSA-9673636
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: KDR: P35968

Reaction (10 results from a total of 11)

Identifier: R-HSA-4088281
Species: Homo sapiens
Compartment: plasma membrane, extracellular region
Endorepellin is the C-terminal domain V of perlecan, constituting amino acids 3687–4391 (Mongiat et al. 2004). It has anti-angiogenic properties, blocking endothelial cell adhesion to fibronectin and type I collagen (Mongiat et al. 2003). Endorepellin and a smaller fragement constituting the third laminin G–like (LG) domain (LG3) disrupt actin stress fibers and focal adhesions via an interaction with the collagen receptor alpha2beta1 integrin (Bix et al. 2004). The first and second laminin G domains 1 of endorepellin bind specifically and with high affinity to Ig domains 3–5 of VEGFR2 (Willis et al. 2013).
Identifier: R-HSA-4420117
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Binding of VEGFA to VEGFR2 induces receptor dimerization and autophosphorylation, leading to the recruitment of downstream signalling molecules. Once the two VEGFR2 receptors are cross-linked to each other, via simultaneous interaction with VEGFA dimer, their membrane-proximal Ig-like domain 7s are held in close proximity so that low-affinity homotypic interactions between these domains further stabilise the receptor dimers. This allows for the exact positioning of the intracellular kinase domains resulting in VEGFR2 autophosphorylation (Ruch et al. 2007, Holmes at al. 2007). The major tyrosine residues known to be autophosphorylated are Y801 and Y951 in the kinase-insert domain, Y1054 and Y1059 within the kinase domain, and Y1175 and Y1214 in the C-terminal tail of VEGFR (Dougher-Vermazen et al. 1994, Cunningham et al. 2007, Kendall et al. 1999, Matsumoto et al. 2005). The Y1175 (mice Y1173) is crucial for endothelial and haemopoietic cell development. Mice with muatation Y1173F die between E8.5 and E9.5 from lack of endothelial and haemopoietic development (Sakurai et al. 2005).
Identifier: R-HSA-4420143
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Two-hybrid mapping showed that tyrosine 951 (Y951) serves as the binding site for T-cell specific adapter molecule (TSAD/ SH2 domain-containing protein 2A (SH2D2A)), also referred as VEGF-receptor-associated protein (VRAP) (Wu et al. 2000). SH2D2A mediates vasular permeability downstream of VEGFR2 by forming a complex with c-SRC (Sun et al. 2012). Site-directed mutation of Y951 to phenylalanine (Y951F) in the VEGFR2, or siRNA mediated silencing of SH2D2A expression, prevented VEGFA mediated cytoskeletal reorganisation and migration but not mitogenicity (Matsumoto et al. 2005).
Identifier: R-HSA-4420202
Species: Homo sapiens
Compartment: plasma membrane
Following tyrosine phosphorylation and activation, PLCG1 dissociates from the VEGFR2 receptor and associates with its substrate phosphatidylinositol (4,5)-bisphosphate (PIP2) in the plasma membrane. PLCG1 hydrolyses PIP2 resulting in the generation of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG is an activator of PKC which leads to subsequent activation of MAP kinase, resulting in increased endothelial cell proliferation. IP3 acts upon receptors in the endoplasmic reticulum causing release of intracellular calcium. Elevation of cytosolic Ca2+ stimulates eNOS to produce nitric oxide (NO) causing vascular dilation. Entry of extracellular calcium through specific channels is important for the activation of certain proteins (Takahashi et al. 2001, Takahashi et al. 1999, Xia et al. 1996).
Identifier: R-HSA-4420153
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Phospholipase C-gamma 1 (PLCG1) plays a pivotal role in angiogenesis and VEGFR2 signal transduction. VEGFR2-mediated activation of PLCG1 in certain endothelial cellular backgrounds is suggested to stimulate cell proliferation and in other endothelial cells to stimulate differentiation and tubulogenesis (Rahimi 2006). Phosphorylated tyrosine 1175 of VEGFR2 provides the binding site for PLCG1, SHC-transforming protein 2 (SHC2/SCK) and SH2 domain-containing adapter protein B (SHB) (Takahashi et al. 2001). Binding of PLCG1 activates protein kinase C (PKC) and this in-turn stimulates mitogen-activated protein (MAP) kinase (MAPK)-dependent pathway and cell proliferation (McLaughlin & Vries 2001).
Identifier: R-HSA-4420107
Species: Homo sapiens
Compartment: plasma membrane, cytosol
Phosphorylated tyrosine Y1175 of VEGFR2 provides the binding site for the adaptor protein SHC-transforming protein 2 (SHC2) also referred as Shc-like protein (SCK). SCK is plausibly involved in coupling VEGFR2 to ERK (Warner et al. 2000, Ratcliffe et al. 2002).
Identifier: R-HSA-194310
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
VEGFR-2 binds VEGF-A, -C, -D, and -E homodimers. VEGFR-2 is the primary mediator of the physiological effects of VEGF-A in angiogenesis, including microvascular permeability, endothelial cell proliferation, invasion, migration, and survival. In endothelial cells, these effects are mediated via activation of a phospholipase gamma-protein kinase C-Raf-MAPK signaling pathway for proliferation and PI3K and focal adhesion kinase for survival and migration. VEGFR-2 is the important receptor among VEGFR protiens and its activation and signaling may be positively or negatively regulated by co-expression and activation of various factors and other VEGF receptors like VEGFR-1 (Hicklin and Ellis 2005).The regulatory events of this receptor will be annotated in subsequent modules.
Identifier: R-HSA-194308
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
VEGFR-3 preferentially binds VEGF-C and -D. Mutations of the VEGFR-3 tyrosine kinase domain are seen in human lymphedema. VEGFR-3 expression has been correlated with transient lymphangiogenesis in wound healing and may modulate VEGFR-2 signaling in maintaining vascular integrity (Hicklin and Ellis 2005).
Identifier: R-HSA-194311
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
VEGFR-1 binds VEGF-A, VEGF-B, and PLGF homodimers. This interaction is required for normal angiogenesis and hematopoiesis, although many of the detailed molecular steps from binding to these physiological consequences remain unclear (Hickins and Ellis, 2005). VEGFR-1 is made up of 1338 aa and has three regions: an extracellular region consisting of 7 immunoglobin-like domains, a transmembrane (TM) domain and a cytosolic tyrosine kinase (TK) domain. An alternatively spliced form, soluble VEGFR-1 (sVEGFR1), also binds VEGF proteins and may serve in the body to down-regulate VEGF activation of membrane-bound receptors. Overexpression of sVEGFR1 (VEGF121) is associated with preeclampsia, a major disorder of pregnancy (Shibuya and Claesson-Welsh 2006; Levine et al. 2004).
Identifier: R-HSA-9691215
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Binding of vascular endothelial growth factor A dimer (VEGFA dimer) to vascular endothelial growth factor receptor 2 dimer (VEGFR2, aka KDR, FLK1) (Ruch et al. 2007) induces receptor dimerization and autophosphorylation, leading to the recruitment of downstream signalling molecules. VEGFA isoform 4 (VEGFA-165) is widely expressed. Signaling through VEGFR2 is the major pathway that activates angiogenesis by inducing the proliferation, survival, sprouting and migration of endothelial cells (ECs), and also by increasing endothelial permeability (Lohela et al. 2009, Shibuya & Claesson-Welsh 2006, Claesson-Welsh & Welsh, 2013).

Complex (1 results from a total of 1)

Identifier: R-HSA-4088279
Species: Homo sapiens
Compartment: plasma membrane
Cite Us!