Molecular Cloning of a Novel Vascular Endothelial Growth Factor, VEGF-D

doi:10.1006/geno.1997.4774

Genomics

Volume 42, Issue 3, 15 June 1997, Pages 483-488

https://doi.org/10.1006/geno.1997.4774 Get rights and content

Abstract

We have identified and characterized a novel vascular endothelial growth factor (VEGF), VEGF-D, which is structurally related to vascular endothelial growth factor C. A full-length cDNA for human VEGF-D was cloned following the identification of an EST obtained through a TFASTA search of public EST databases. The murine VEGF-D was subsequently isolated from a mouse lung cDNA library. The human VEGF-D gene was mapped to human chromosome Xp22.31. Both human and mouse VEGF-D are strongly expressed in lung and encode the eight cysteine residues that are highly conserved among the members of this family. The high level of conservation between mouse and human VEGF-D may emphasize the biological importance of this gene. Recently the murine gene, FIGF, which is identical to mouse VEGF-D, was reported.

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Citation Excerpt :
Not surprisingly, the lack of increase in VEGFR-3 signaling can be explained given the knowledge that the cysteine mutation at residue 117 results in different effects on the receptors, depending on protein concentration.19 Human FIGF is expressed in the lung before birth,23 and in adults in the heart, lung, skeletal muscle, and intestine11,20; it has recently been shown to play important roles in pulmonary vascular leak in response to hyperoxia.24 The grandfather's respiratory findings may reflect a mild disease phenotype consistent with variable expressivity or incomplete penetrance, and carriers of the gene change may show minimal, if any, phenotype; we cannot rule out as yet unidentified modifying genes or other factors to explain the disparate phenotypic findings between grandfather and grandson.
Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos–induced growth factor) gene encoding VEGF-D have not been reported previously. We describe a young male with a hemizygous mutation in the X-chromosome gene FIGF (c.352 G>A) associated with early childhood respiratory deficiency. Histologically, lungs showed ectatic pulmonary arteries and pulmonary veins. The mutation resulted in a substitution of valine to methionine at residue 118 of the VEGF-D protein. The resultant mutant protein had increased dimerization, induced elevated VEGFR-2 signaling, and caused aberrant angiogenesis in vivo. Our observations characterize a new subtype of congenital diffuse lung disease, provide a histological correlate, and support a critical role for VEGF-D in lung vascular development and homeostasis.
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Citation Excerpt :
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¹: To whom correspondence should be addressed. Telephone: 81-298-30-6211. Fax: 81-298-30-6270. E-mail: [email protected].

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Regular ArticleMolecular Cloning of a Novel Vascular Endothelial Growth Factor, VEGF-D

Abstract

Blood

J. Biol. Chem.

J. Biol. Chem.

Cell

Genomics

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Cell

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders

N. Engl. J. Med.

A second signal supplied by insulin-like growth factor II in oncogene-induced tumorigenesis

Nature

The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor

Science

Aortic smooth muscle cells express and secrete vascular endothelial growth factor

Growth Factors

Platelet-derived growth factor-induced transcription of the vascular endothelial growth factor gene is mediated by protein kinase C

Cancer Res.

The Fos complex and Fos-related antigens recognize sequence elements that contain AP-1 binding sites

Science

Regular Article
Molecular Cloning of a Novel Vascular Endothelial Growth Factor, VEGF-D