Kdr (rat VEGFR-2 / Flk-1; UniProt O08775) - manual literature synthesis

No deep-research provider was available for this review. This file was written by hand
from the cached publications in publications/, the rat UniProt record
(Kdr-uniprot.txt) and QuickGO look-ups of the human (P35968) and mouse (P35918)
orthologs, which are the donors for most ISO/ISS rows. Provenance is given inline.

Identity

• Rat Kdr (RGD:2965, GeneID 25589) encodes vascular endothelial growth factor receptor 2,
  a 1343-aa single-pass type I receptor tyrosine kinase of the CSF-1/PDGF receptor
  subfamily [UniProtKB:O08775 "Belongs to the protein kinase superfamily. Tyr protein
  kinase family. CSF-1/PDGF receptor subfamily."].
• Seven extracellular Ig-like domains (D2-D3 bind ligand), a transmembrane helix, a split
  tyrosine kinase domain with a kinase insert, and a C-terminal tail carrying docking
  phosphotyrosines [UniProtKB:O08775 "The second and third Ig-like C2-type
  (immunoglobulin-like) domains are sufficient for VEGFC binding"].

Molecular function

• VEGF receptor activity: ligand (VEGFA, VEGFC, VEGFD) binding drives dimerization and
  trans-autophosphorylation [UniProtKB:O08775 "Binding of VEGFA, VEGFC or VEGFD leads to
  dimerization and activation by autophosphorylation on tyrosine residues"].
• Rat-specific experiments: cloning of rat Flk-1 from retina; both the full-length and a
  short form lacking the C-terminal half of the kinase domain bind VEGF and signal Ca2+
  PMID:9442048.
• Maturation and substrate: only the mature, fully glycosylated 230 kDa cell-surface form
  is tyrosine phosphorylated on VEGF stimulation, and PLC-gamma is the major substrate
  [PMID:9160888 "Only this 230 kDa form was rapidly and transiently phosphorylated on
  tyrosine residues in the presence of VEGF"; "As a major substrate of KDR/Flk-1,
  PLC-gamma was found to be rapidly tyrosine-phosphorylated and associated with
  KDR/Flk-1"]. (Assay cells in the abstract are endothelial and NIH3T3; species of the
  receptor not stated in the abstract.)

Signalling outputs

• PLCG1 -> DAG/IP3/PKC; ERK1/2 MAPK; PI3K-AKT; FAK; eNOS/NO (UniProt FUNCTION, by
  similarity to human P35968).
• In rat neurons VEGF raises cytosolic Ca2+ and activates CaMKII, CREB, ERK and mTOR in a
  VEGFR2-dependent way and enhances long-term synaptic transmission PMID:18221855.
• Rat spinal motor neuron survival under hypoxia needs Flk-1 (antisense knock-down) acting
  via PI3K/Akt and MEK/ERK PMID:15780476.
• VEGF neurite outgrowth from rat cortical neurons via VEGFR2 and Rho/ROK PMID:16329123.
• Dominant-negative KDR blocks hippocampal neurogenesis and learning in adult rats
  PMID:15258583; Flk-1 signalling required for antidepressant-induced proliferation
  PMID:17360578.

Vascular physiology (rat)

• KDR is the predominant receptor for VEGF-induced vasodilation and hypotension in
  conscious rats PMID:12052848.
• KDR kinase inhibitors block laser-induced choroidal and oxygen-induced retinal
  neovascularization in rats PMID:15951738; anti-VEGFR2 antibody TTAC-0001 blocks
  sprouting of rat aortic rings PMID:25942475.
• Testis: VEGFR inhibitors disrupt seminiferous cord formation and vascularization in
  cultured E13 rat testes; KDR protein in germ and interstitial cells PMID:16672722.

Expression-only papers

• Flk-1 up-regulated in vessels and neurons after VEGF infusion trauma / brain contusion
  [PMID:11934468; PMID:15785231].
• Retinal ganglion cell layer Vegfr-2 mRNA is high at baseline and essentially unchanged
  after optic nerve transection except for a decrease at 6 h PMID:20187850.
• PMID:15885787 is a human pterygium/conjunctiva study (patient tissue), not rat.
• PMID:20097747 (hyaluronan butyric/retinoic ester, HBR, infarcted rat heart): HBR
  raises kdr mRNA in rat cardiomyocytes and Stro-1 cells PMID:20097747. This is expression regulation of Kdr, not a function of the Kdr protein.

Ortholog donor provenance (QuickGO, 2026-10-28)

• Mouse Kdr: coreceptor activity and semaphorin-plexin signalling rest on an IGI with
  SEMA3E (PMID:25985275); cytokine binding is an IPI with gremlin-1 (Grem1, O70326,
  PMID:20660291); calcium ion homeostasis IDA PMID:8356051; surfactant homeostasis and
  cell maturation IMP PMID:12053176; lung/epithelial branching IMP PMID:16375885.
• Human KDR: cytosol is an HPA immunofluorescence IDA; macroautophagy, mitochondrial
  depolarization and mitochondrial fission are MGI IGI rows from PMID:23798385;
  negative regulation of gene expression and cellular response to H2S from PMID:26879375.