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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A family of growth arrest specific (Gas) genes was operationally defined on the basis of the strategy utilized to isolate them e.g. differential expression in quiescent and growing cells. Our interest in the Gas-3 gene was prompted by our previously reported localization of the gene on the mouse chromosome 11.44 +/- 1.9 cM proximal to the Trp53 locus and by the finding, by others, that it codes for a myelin protein and that a point mutation in its fourth putative transmembrane region is associated with the trembler mutation. We have isolated the human homologous of the mouse Gas-3 gene and utilized the cloned sequences as a probe to localize the gene on human chromosomes both by analysis of human-rodent somatic cell hybrids and in situ hybridization of human metaphases. We have now localized the human Gas-3 gene on chromosome 17p12-13. Its possible role in both the development of neoplasia in neurofibromatosis patients and in the myelin degenerative disease as the Charcot-Marie-Tooth is discussed.
Hum Mol Genet 1992 Aug
PMID:Isolation and mapping to 17p12-13 of the human homologous of the murine growth arrest specific Gas-3 gene. 130 10

BXH-2 mice have the highest incidence of spontaneous retrovirally induced myeloid leukemia of any known inbred strain and, as such, represent a valuable model system for identifying cellular proto-oncogenes involved in myeloid disease. Chronic murine leukemia viruses often induce disease by insertional activation or mutation of cellular proto-oncogenes. These loci are identified as common viral integration sites in tumor DNAs. Here we report on the characterization of a novel common viral integration site in BXH-2 myeloid leukemias, designated Evi-2. Within the cluster of viral integration sites that define Evi-2, we identified a gene that has the potential for encoding a novel protein of 223 amino acids. This putative proto-oncogene possesses all of the structural features of a transmembrane protein. Within the transmembrane domain is a "leucine zipper," suggesting that Evi-2 is involved in either homopolymer or heteropolymer formation, which may play an important role in the normal functioning of Evi-2. Interestingly, the human homolog of Evi-2 has recently been shown to be tightly linked to the von Recklinghausen neurofibromatosis locus, suggesting a role for Evi-2 in human disease as well.
Mol Cell Biol 1990 Sep
PMID:Evi-2, a common integration site involved in murine myeloid leukemogenesis. 216 36

The present study was undertaken to investigate whether vascular cells show insulin-like growth factor I (IGF-I; somatomedin C) immunoreactivity under normal conditions and/or during angiogenesis in humans and animals, as the trophic peptide IGF-I is considered important for cell growth and differentiation. In adult animals normal blood vessels, i.e., arteries, veins, and capillaries, did not show any IGF-I immunoreactivity. In newborn animals every vascular cell showed IGF-I immunoreactivity; the frequency and intensity thereafter decreased and eventually vanished as the animals approached maturity. Injury of a tissue or organ rapidly induced extensive blood vessel formation and such new blood vessels transiently expressed IGF-I immunoreactivity. Endothelial cells in budding capillaries showed distinct cytoplasmic IGF-I immunoreactivity, as did endothelial cells, smooth muscle cells, and fibroblast in newly formed arteries and veins. In biopsies of human tissue, transient IGF-I immunoreactivity was evident in vascular cells during angiogenesis after injury, as it also was in granulation tissue, skin wounds, and scar capsules around implants. Increased IGF-I immunoreactivity was further demonstrated in vascular cells in biopsies from patients with other changes involving blood vessel formation, e.g., nasal polyps, and in specimens from patients with arteritis, tendonitis, synovitis, Wegener's granulomatosis, idiopathic midline destructive disease, neurofibromatosis (von Recklinghausen's disease), and muscular dystrophy. It is concluded that during angiogenesis, obviously irrespective of inducing factors and mechanisms, vascular wall cells transiently show IGF-I immunoreactivity.
Exp Mol Pathol 1989 Feb
PMID:Transient expression of insulin-like growth factor I immunoreactivity by vascular cells during angiogenesis. 246 16

The neurofibromatosis 2 (NF2) gene product, merlin, encodes a 595 amino acid protein with sequence similarity to a family of proteins linking cell membrane proteins to the cytoskeleton. Two isoforms of merlin have been described which differ by the presence (type 2 merlin) or absence (type 1 merlin) of exon 16 sequences inserted into the extreme carboxyl terminus of the protein. To determine the role of this important negative growth regulator during normal embryonic development, the expression of these two merlin isoforms was examined at representative stages of rat embryogenesis and in adult tissues. Partial sequence analysis of the rat merlin gene demonstrated striking amino acid identity to the published mouse and human merlin gene sequences. In situ hybridization and RT-PCR analyses demonstrated that rat merlin is widely expressed during embryogenesis and early postnatal life in most tissues but becomes restricted to the brainstem, cerebellum, dorsal root ganglia, spinal cord, adrenal gland and testis in adult animals. The elucidation of the pattern of merlin gene expression in adult and embryonic tissues provides the foundations for future studies aimed at determining the function(s) of this protein during cell differentiation and embryonic development.
Hum Mol Genet 1995 Mar
PMID:Expression of the neurofibromatosis 2 (NF2) gene isoforms during rat embryonic development. 779 5

Using a yeast two-hybrid system, we identified a novel protein which interacts with ras p21. This protein shares 69% amino acid homology with ral guanine nucleotide dissociation stimulator (ralGDS), a GDP/GTP exchange protein for ral p24. We designated this protein RGL, for ralGDS-like. Using the yeast two-hybrid system, we found that an effector loop mutant of ras p21 was defective in interacting with the ras p21-interacting domain of RGL, suggesting that this domain binds to ras p21 through the effector loop of ras p21. Since ralGDS contained a region highly homologous with the ras p21-interacting domain of RGL, we examined whether ralGDS could interact with ras p21. In the yeast two-hybrid system, ralGDS failed to interact with an effector loop mutant of ras p21. In insect cells, ralGDS made a complex with v-ras p21 but not with a dominant negative mutant of ras p21. ralGDS interacted with the GTP-bound form of ras p21 but not with the GDP-bound form in vitro. ralGDS inhibited both the GTPase-activating activity of the neurofibromatosis gene product (NF1) for ras p21 and the interaction of Raf with ras p21 in vitro. These results demonstrate that ralGDS specifically interacts with the active form of ras p21 and that ralGDS can compete with NF1 and Raf for binding to the effector loop of ras p21. Therefore, ralGDS family members may be effector proteins of ras p21 or may inhibit interactions between ras p21 and its effectors.
Mol Cell Biol 1994 Nov
PMID:ralGDS family members interact with the effector loop of ras p21. 793 63

Schwannomas are common tumors of the nervous system and are frequently found in patients with neurofibromatosis (NF) 2. Although loss of heterozygosity in NF2 tumors suggests that the NF2 gene functions as a tumor suppressor gene, the NF2 gene shows amino acid sequence homology to structural proteins in one of which dominantly acting mutations have been described. We performed a mutational analysis in 30 vestibular schwannomas and examined the effect of mutations on the NF2 protein. We detected 18 mutations in 30 vestibular schwannomas of which seven contained loss or mutation of both NF2 alleles. Most mutations were predicted to result in a truncated protein. Mutational hot spots were not identified. Immunocytochemical studies using antibodies to the NF2 protein showed complete absence of staining in tumor Schwann cells, whereas staining was observed in normal vestibular nerve. These data indicate that loss of NF2 protein function is a necessary step in schwannoma pathogenesis and that the NF2 gene functions as a recessive tumor suppressor gene.
Hum Mol Genet 1994 Jun
PMID:Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas. 795 Dec 31

We previously described a patient with neurofibromatosis type 2 (NF2) who showed a constitutional balanced translocation, t(4;22). To characterize the breakpoint on chromosome 22 in this patient in relation to a candidate gene (NF2) responsible for NF2, we analyzed DNAs from this patient and her parents using parts of NF2 cDNA as probes. Southern analyses and DNA sequencing revealed that the chromosome 22 breakpoint in this patient lies within the intron between exons 14 and 15 of NF2. The results lend support to the conclusion that NF2 is the gene responsible for the CNS form of neurofibromatosis.
Hum Mol Genet 1994 Jun
PMID:Characterization of the translocation breakpoint on chromosome 22q12.2 in a patient with neurofibromatosis type 2 (NF2). 795 Dec 41

Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, caused by mutations in the NF-1 gene. Mutation analysis in the NF-1 gene is complicated by the large size of the gene, the high mutation rate, and the presence of pseudogenes. By means of the polymerase chain reaction, we have amplified 70% of the NF-1 coding sequence using reverse transcribed mRNA and genomic DNA from 25 unrelated Scottish Caucasian patients. We have used chemical mismatch cleavage analysis and direct sequencing of asymmetrically amplifed PCR products to characterise mutations within the NF-1 gene. Using the above strategy, we detected 10 novel mutations and an intragenic polymorphism with a heterozygosity of approximately 47% in the Scottish population. Of the 10 mutations, 7 are potentially disease causing. They include splice site errors responsible for exon skipping (1721 + 3A to G) and (5749 + 2T to G), small insertions (7485insGG) and (6519insG), a nonsense mutation (R2496X), and missense and silent mutations (G1166D, K1419R, G1404G, S1311S, N1776N). A correlation of the phenotype with the genotype is presented. Thus, in this study we have identified a heterogeneous group of germline mutations, the majority of which are predicted to cause disruption of the protein product, neurofibromin. This approach has therefore proved to be useful for the detection of mutations in the gene for neurofibromatosis type-1, and can be applied to detection of molecular pathologies in general.
Hum Mol Genet 1994 Jul
PMID:Characterisation of inherited and sporadic mutations in neurofibromatosis type-1. 798 79

Family studies and tumor analyses have combined to indicate that neurofibromatosis 2 (NF2), a disorder characterized by multiple benign tumors of the nervous system, and sporadic non-inherited forms of the same tumor types are both caused by inactivation of a tumor suppressor gene located in 22q12. Recently, the gene encoding merlin, a novel member of a family of cytoskeleton-associated proteins, was identified as the NF2 tumor suppressor. To facilitate the search for merlin mutations, we have defined the exon-intron boundaries for all 17 NF2 exons, including one subject to alternative splicing. We have developed polymerase chain reaction assays to amplify each exon from genomic DNA, and used these assays to perform single-strand conformation polymorphism analysis of DNA from 30 sporadic and eight NF2-derived schwannomas, the hallmark tumor type in this disorder. Of a maximum of 60 alleles scanned, 32 showed mutations affecting expression of the merlin protein. Thirty of these mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal splicing, while two are missense mutations. Thus, inactivation of merlin is a common feature underlying both inherited and sporadic forms of schwannoma.
Hum Mol Genet 1994 Mar
PMID:Exon scanning for mutation of the NF2 gene in schwannomas. 801 53

In order to permit detailed characterization of meningioma cases showing deletions within chromosomal band 22q12 and further systematically clone genes located within this region, we established a genomic YAC and cosmid contig which encompasses a region in excess of 1000 kb of 22q12. The YAC contig consists of 6 YAC clones arranged into 5 overlapping steps covering more than 1100 kb. Two corresponding cosmid contigs consisting of 40 steps of overlapping groups of cosmids encompasses 900-1000 kb. This set of genomic clones provides a detailed physical map of this part of chromosome 22 and constitutes a basis for the isolation and characterization of genes that may be located within this chromosomal region. Employing the exon-amplification method on two cosmids from the contig, we cloned a novel, anonymous gene, pK1.3, which potentially encodes a protein of 683 amino acids with a predicted molecular weight of of 78.5 kD. Its 2.7 kb mRNA is expressed ubiquitously. We estimated the genomic size of this gene to 100-150 kb, and it is located in the immediate centromeric vicinity of the neurofibromatosis 2 (NF2) tumor suppressor gene.
Hum Mol Genet 1993 Sep
PMID:Cloning of a novel, anonymous gene from a megabase-range YAC and cosmid contig in the neurofibromatosis type 2/meningioma region on human chromosome 22q12. 824 58


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