Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap exchange factor.

Ras proteins operate as molecular switches in signal transduction pathways downstream of tyrosine kinases and G-protein-coupled receptors. Ras is switched from the inactive GDP-bound state to the active GTP-bound state by guanine nucleotide exchange factors (GEFs). We report here the cloning and characterization of RasGRP2, a longer alternatively spliced form of the recently cloned RapGEF, CalDAG-GEFI.

Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia.

Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generated Vegfb knockout mice (Vegfb(-/-)). Unlike Vegfa knockout mice, which die during embryogenesis, Vegfb(-/-) mice are healthy and fertile.

A 500-kb sequence-ready cosmid contig and transcript map of the MEN1 region on 11q13.

We have generated a transcript map of an approximately 1.2-Mb region from human chromosome band 11q13 between the loci VEGFB and CAPN1, which flank the multiple endocrine neoplasia type 1 (MEN 1) locus. In total, we isolated 144 cosmids from this region and generated a sequence-ready cosmid contig of the approximately 500-kb region between the neurexin locus and D11S2196E.

Characterization of the mouse Men1 gene and its expression during development.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1), a heritable predisposition to endocrine tumours in man, has recently been identified. Here we have characterized the murine homologue with regard to cDNA sequence, genomic structure, expression pattern and chromosomal localisation. The murine Men1 gene spans approximately 6.

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear.

Characterisation of a new human and murine member of the DnaJ family of proteins.

We report the characterisation of a human gene, designated MCG18 (multiple endocrine neoplasia type 1 candidate gene 18), that encodes a new member of the DnaJ family of proteins. Database searches indicate that MCG18 also has the locus name HSPF2. MCG18 lies 250bp centromeric of the VRF/VEGFB gene on chromosome 11q13.

Analysis of the promoter region of the human VEGF-related factor gene.

We have characterised the promoters of the human and murine VRF (vascular endothelial growth factor (VEGF) related factor) gene. A series of deletions were made of a 553-bp region 5' of the VRF initiation codon and were used in a luciferase reporter gene assay to determine the minimal promoter of the VRF gene. The region between base pairs -443 and -195 was sufficient to mediate transcription in lymphocytes and the region between -550 and -443 enhanced this promoter activity.

Characterization of the murine VEGF-related factor gene.

We describe here the molecular cloning and characterization of the murine homolog of the human vascular endothelial growth factor-related factor (VRF) gene. cDNAs for two alternatively spliced forms of the murine vrf gene have been isolated, the putative translation products of which differ at their carboxyl termini due to a shift in reading frame caused by insertion, or lack thereof, of exon 6, in a similar fashion to human VRF (hVRF). The message lacking exon 6 encodes a protein (mvrf167) with 86% identity and 92% conservation of amino acid residues with hVRF.

Characterisation of genes encoding a nucleoside monophosphate kinase and a L35 ribosomal protein from Babesia bovis.

We have sequenced a region of the Babesia bovis nuclear genome that encodes a L35 ribosomal protein homologue (bl35) and a putative nucleoside monophosphate kinase (bnmk) that is most similar to the adenylate kinase of gram-positive bacteria and the mitochondrial form of adenylate kinase in eukaryotes. BNMK appears to be unique in that it is the first eukaryotic family member to feature a putative zinc-binding domain. bnmk and bl35 are closely linked and transcribed from opposite DNA strands.

Cloning and characterization of a novel human gene related to vascular endothelial growth factor.

This paper describes the cloning and characterization of a new member of the vascular endothelial growth factor (VEGF) gene family, which we have designated VRF for VEGF-related-factor. Sequencing of cDNAs from a human fetal brain library and RT-PCR products from normal and tumor tissue cDNA pools indicate two alternatively spliced messages with open reading frames of 621 and 564 bp, respectively. The predicted proteins differ at their carboxyl ends resulting from a shift in the open reading frame.