VEGF Receptors

VEGF receptors have been classified in three groups; VEGFR-1 (flt-1), VEGFR-2 (KDR/flk-1), and VEGFR-3 (flt-4) (see Figure 1). VEGFR-1 and VEGFR-2 are predominantly expressed on vascular endothelial cells. VEGFR-3 is expressed on vascular and lymphatic endothelial cells during embryogenesis, but at later stages is expressed only on lymphatic endothelium. The receptors possess intra-cellular domains containing ligand-stimulatable tyrosine kinase, a single hydrophobic transmembrane-spanning membrane, and extracellular domains comprising seven immunoglobulin-like loops. Extracellular domains of VEGFR-3 contain a disulfide bridge, whereas VEGFR-1 and VEGFR-2 do not, which may explain their different binding abilities.

VEGF-A reveals high-affinity binding to both VEGFR-1 and VEGFR-2. VEGF-B and PlGF bind with high affinity to VEGFR-1 only, whereas VEGF-E binds to VEGFR-2 only. VEGF-C and VEGF-D bind to VEGFR-2 and VEGFR-3.

In addition, some types of VEGF bind to co-receptors; PlGF binds to neuropilin-1, and VEGF165 to neuropilin-1

and neuropilin-2. The association of VEGF1

with neuropilin-1 has been reported to increase the affinity of VEGF165 with VEGFR-2 about tenfold, resulting in VEGF165 being the strongest signal transducer among the VEGF subtypes.

VEGF-A

VEGF-A

Figure 1 Family of VEGF receptors. The diagram illustrates the interaction of VEGF with the family of VEGF receptors, VEGFR-1 (flt-1), VEGFR-2 (KDR/flk-1), and VEGFR-3 (flt-4). The receptors possess intracellular domains containing ligand-stimulatable tyrosine kinase, a single hydrophobic transmembrane-spanning membrane, and extracellular domains comprising seven immunoglobulin-like loops. Extracellular domains of VEGFR-3 contain a disulfide bridge, whereas VEGFR-1 and VEGFR-2 do not. VEGF-A binds to both VEGFR-1 and VEGFR-2. VEGF-B and PlGF bind with high affinity to VEGFR-1 only, whereas VEGF-E binds to VEGFR-2 only. VEGF-C and VEGF-D bind to VEGFR-2 and VEGFR-3. Neuropilin is a co-receptor for some types of VEGF: PlGF binds with neuropilin-1, and VEGF165 with neuropilin-1 and neuropilin-2. (G. Neufeld et al. FASEB J. 1999)

VEGFR-1 VEGFR-2 VEGFR-3 Neuroplilin-1 Neuroplilin-2 (flt-1) (KDR/flk-1) (flt-4)

Figure 1 Family of VEGF receptors. The diagram illustrates the interaction of VEGF with the family of VEGF receptors, VEGFR-1 (flt-1), VEGFR-2 (KDR/flk-1), and VEGFR-3 (flt-4). The receptors possess intracellular domains containing ligand-stimulatable tyrosine kinase, a single hydrophobic transmembrane-spanning membrane, and extracellular domains comprising seven immunoglobulin-like loops. Extracellular domains of VEGFR-3 contain a disulfide bridge, whereas VEGFR-1 and VEGFR-2 do not. VEGF-A binds to both VEGFR-1 and VEGFR-2. VEGF-B and PlGF bind with high affinity to VEGFR-1 only, whereas VEGF-E binds to VEGFR-2 only. VEGF-C and VEGF-D bind to VEGFR-2 and VEGFR-3. Neuropilin is a co-receptor for some types of VEGF: PlGF binds with neuropilin-1, and VEGF165 with neuropilin-1 and neuropilin-2. (G. Neufeld et al. FASEB J. 1999)

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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