Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone, Vgr-2, with homology to certain members of the transforming growth factor-beta superfamily has been isolated from a mouse embryo cDNA library. The encoded protein shows significant similarity to members of the Vg-1/decapentaplegic/bone morphogenetic protein subgroup of the transforming growth factor-beta family. Within this group, Vgr-2 is more similar to Xenopus Vg-1 than to any other member so far isolated. The gene is expressed at highest levels during midgestation mouse development, and transcripts are localized by in situ hybridization to the osteogenic zone of developing bone. Vgr-2 is expressed in F9 teratocarcinoma cells, and its RNA levels are down-regulated within 24 h after differentiation with retinoic acid. The genomic organization of Vgr-2 and its location on mouse chromosome 6 are reported.
Mol Endocrinol 1992 Nov
PMID:Isolation of Vgr-2, a novel member of the transforming growth factor-beta-related gene family. 148 Jan 82

The effects of porcine bone morphogenetic protein (BMP) on DNA and collagen synthesis in cultured rat osteogenic sarcoma cells and mink lung epithelial cells were studied and compared with the effects induced by transforming growth factor-beta 1 (TGF-beta 1). In both cells, DNA synthesis was slightly but significantly increased by BMP whereas it was notably decreased by TGF-beta 1. The inhibitory action of TGF-beta 1 overrode the activation of DNA synthesis by BMP when the cells were incubated together with TGF-beta 1 and BMP. In osteogenic sarcoma cells, collagen synthesis was enhanced by both BMP and TGF-beta 1, but the stimulatory action of BMP was weaker than that of TGF-beta 1. In epithelial cells, TGF-beta 1 increased collagen synthesis but BMP induced no significant changes. No synergistic effects of TGF-beta 1 and BMP on collagen synthesis were observed in both cells. The present study demonstrates the possibility of direct actions of BMP and TGF-beta 1 on cultured rat osteogenic sarcoma cells and mink lung epithelial cells in vitro.
Biochem Mol Biol Int 1994 May
PMID:Differential effects of transforming growth factor-beta 1 and bone morphogenetic proteins in cultured rat osteogenic sarcoma and mink lung epithelial cells. 795 Oct 46

We have obtained trigonal crystals of recombinant human osteogenic protein-1 (hOP-1), a member of the transforming growth factor-beta (TGF-beta) superfamily. hOP-1 (also referred to as BMP-7) is a bone morphogenetic protein and is active as a dimer of M(r) 32 to 36 kDa. The crystals have the symmetry of space group P3(1)21 or the enantiomorph P3(2)21 with unit cell dimensions of a = b = 99.46 A, c = 42.09 A. The crystals diffract to 2.2 A resolution and there is one hOP-1 monomer per asymmetric unit. In this paper we describe the first crystallization of a bone morphogenetic protein and present the results of preliminary X-ray diffraction data from the native protein and two heavy-atom derivatives.
J Mol Biol 1994 Dec 16
PMID:Crystallization and preliminary crystallographic data of recombinant human osteogenic protein-1 (hOP-1). 799 Jan 48

A possible interaction between tumor necrosis factor (TNF) and transforming growth factor-beta (TGF-beta) superfamily cytokines in stimulating the production of nerve growth factor (NGF) in Swiss 3T3 cells was studied. Although TGF-beta 1 and Activin A stimulated NGF production in Swiss 3T3 cells, they antagonized the stimulatory effect of TNF on fibroblast NGF production when used in combination. On the contrary, TNF's stimulatory activity on fibroblast NGF production was markedly synergized by bone morphogenetic protein-2 (BMP-2); BMP-2 by itself did not stimulate NGF production in the cells. These findings suggest that BMP-2, in concert with TNF, plays an essential role in regulating the regeneration of peripheral nerves following injury with bone fracture through an indirect mechanism by which it stimulates NGF production in fibroblasts.
Biochem Mol Biol Int 1996 May
PMID:Bone morphogenetic protein-2 is markedly synergistic with tumor necrosis factor in stimulating the production of nerve growth factor in fibroblasts. 873 30

Expression of bone morphogenetic protein (BMP)-2 mRNA was stimulated by retinoic acid in human adenocarcinoma cell line, HSG-S8, in a dose-dependent manner. Northern blot analysis demonstrated that retinoic acid most strongly increased the level of BMP-2 mRNA 6 h after the treatment and the stimulatory effect was maintained at 48 h. The mature peptides of 16 and 18 kDa molecular masses of BMP-2 were also increased in the conditioned medium by the treatment of retinoic acid on western blotting. The proliferation of HSG-S8 cells was inhibited by retinoic acid, however, retinoic acid did not cause morphological change showing cellular differentiation. 1 alpha, 25(OH)2D3, like retinoic acid, clearly increased the mRNA level of BMP-2, whereas dibuthryl cyclic AMP remarkably diminished it, and bromodeoxyuridine had no effect on the expression of BMP-2 mRNA.
Biochem Mol Biol Int 1996 May
PMID:Retinoic acid enhances expression of bone morphogenetic protein-2 in human adenocarcinoma cell line (HSG-S8). 873 45

The shape of collagen fibrils growing in vitro in a cell-free enzyme/substrate system is shown to be dependent on the enzyme/substrate (E/S) ratio. Long fibrils with tapered ends were generated by exposing pCcollagen (procollagen from which the N-propeptides had been removed) to procollagen C-proteinase (which acts by cleaving the C-propeptides from the pCcollagen, converting it to insoluble fibril-forming collagen). Tip shape profiles, established quantitatively by scanning transmission electron microscopy, depended critically on the C-proteinase/pCcollagen ratio. The finest tips occurred at low ratios, the coarsest at high ratios. All fibrils had molecules oriented with amino termini closest to the pointed ends, i.e. N,N-bipolar fibrils in which molecules change orientation abruptly at one location along the fibril. Fibrils had maximal diameter at this molecular switch region. Shape asymmetric fibrils occurred at low E/S ratios, near-shape symmetric fibrils occurred at high ratios. Fibrils generated at low E/S ratios bore the closest resemblance to those formed in vivo except that the central shaft regions of fibrils formed in vitro showed no tendency to be limited to a uniform diameter.
J Mol Biol 1996 Aug 16
PMID:Enzymic control of collagen fibril shape. 875 78

Recombinant human bone morphogenetic protein (rhBMP-2) was examined for its in vitro effects on biochemical markers representing osteoblast phenotype. Primary cultures of fetal rat calvarial osteoblasts were used in this study. The results indicated that rhBMP-2 stimulated alkaline phosphatase activity, parathyroid hormone (PTH)-induced cyclic AMP production, and collagen biosynthesis in a dose-dependent manner in confluent cultures. The percent collagen synthesis also increased in a dose-dependent manner. Alkaline phosphatase activity was stimulated in a time-dependent manner by rhBMP-2 that reached its maximum 5 days after initiation. Cycloheximide (2 micrograms/ml) inhibited rhBMP-2-stimulated alkaline phosphatase indicating de novo protein synthesis of the enzyme. Transforming growth factor-beta 1 (TGF-beta 1)-induced inhibition of alkaline phosphatase activity observed in confluent primary cultures was completely abolished by rhBMP-2 at a concentration that was 43 times greater than the TGF-beta 1 concentration. Also, rhBMP-2 produced a small stimulation of alkaline phosphatase activity in cells grown in the absence of ascorbic acid; however, the effect was greatly enhanced in cells cultivated in the presence of ascorbic acid (50 micrograms/ml). In view of the potentiating effect of ascorbic acid on rhBMP-2-induced stimulation of alkaline phosphatase, we speculate that ascorbic acid could amplify the osteoinductive effects of rhBMP-2 and thereby augment the efficacy of the BMP when used as bone repair material in vivo. rhBMP-2 (4.3-86 ng/ml) did not exhibit mitogenic effects on cultured osteoblasts. These data suggest that rhBMP-2 has the ability to induce expression of various markers associated with the osteoblast phenotype in primary cultures of fetal rat calvarial osteoblasts. In addition, we speculate that TGF-beta 1 may play a regulatory role in BMP-induced bone formation and ascorbic acid may potentiate the effects of rhBMP-2 in vivo.
Mol Cell Biochem 1997 Feb
PMID:Recombinant human bone morphogenetic protein-2 stimulates differentiation in primary cultures of fetal rat calvarial osteoblasts. 905 79

Bone morphogenetic proteins induce chondrogenesis and osteogenesis in vivo. To investigate molecular mechanisms involved in chondrocyte induction, we examined the effect of osteogenic protein (OP)-1/bone morphogenetic protein-7 on the collagen X promoter. In rat calvaria-derived chondrogenic C5.18 cells, OP-1 up-regulates collagen X mRNA levels and its promoter activity in a cell type- specific manner. Deletion analysis localizes the OP-1 response region to 33 bp (-310/-278), which confers OP-1 responsiveness to both the minimal homologous and heterologous Rous sarcoma virus promoter. Transforming growth factor-beta2 or activin, which up-regulates the expression of a transforming growth factor-beta-inducible p3TP-Lux construct, has little effect on collagen X mRNA and on this 33-bp region. Mutational analysis shows that both an AP-1 like sequence (-294/-285, TGAATCATCA) and an A/T-rich myocyte enhancer factor (MEF)-2 like sequence (-310/-298, TTAAAAATAAAAA) in the 33-bp region are necessary for the OP-1 effect. Gel shift assays show interaction of distinct nuclear proteins from C5.18 cells with the AP-1-like and the MEF-2-like sequences. OP-1 rapidly induces nuclear protein interaction with the MEF-2-like sequence but not with the AP-1 like sequence. MEF-2-like binding activity induced by OP-1 is distinct from the MEF-2 family proteins present in C2C12 myoblasts, in which OP-1 does not induce collagen X mRNA or up-regulate its promoter activity. In conclusion, we identified a specific response region for OP-1 in the mouse collagen X promoter. Mutational and gel shift analyses suggest that OP-1 induces nuclear protein interaction with an A/T-rich MEF-2 like sequence, distinct from the MEF-2 present in myoblasts, and up-regulates collagen X promoter activity, which also requires an AP-1 like sequence.
Mol Endocrinol 1997 Nov
PMID:Osteogenic protein-1 up-regulation of the collagen X promoter activity is mediated by a MEF-2-like sequence and requires an adjacent AP-1 sequence. 936 51

Expression of the receptor tyrosine kinase, Trk, determines the specificity of neurotrophin responsiveness of different neuronal populations during development. Recently it has become apparent that sympathetic neurons of rat superior cervical ganglia (SCG) acquire sensitivity to neurotrophin-3 (NT3) before they become dependent on the target-derived nerve growth factor (NGF) for their survival by sequential induction of TrkC and TrkA. The mechanism controlling the expression of TrkC as well as the source of NT3 at their initial developmental stage has, however, not been clarified. Here we show that the treatment of the perinatal rat SCG neurons which express high levels of trkA mRNA with bone morphogenetic protein-2 (BMP2) induced the expression of trkC mRNA. Induction of the functional TrkC receptor by BMP2 was confirmed by the enhancement of the survival response of these neurons to NT3. Treatment of SCG neurons with retinoic acid (RA) promoted the effect of BMP2 on the induction of trkC mRNA levels. BMP2 treatment, on the other hand, promoted the effect of RA on the suppressions of trkA mRNA levels and the NGF-dependent survival of the SCG neurons. Furthermore, BMP2/RA treatment induced the endogenous expression of NT3. These results indicate that specific environmental signals can regulate neurotrophin responsiveness of developing sympathetic neurons by differential alteration of the trk and neurotrophin expressions.
Brain Res Mol Brain Res 1998 Jan
PMID:Bone morphogenetic protein-2 and retinoic acid induce neurotrophin-3 responsiveness in developing rat sympathetic neurons. 947 74

The human bone morphogenetic protein-1 was originally identified as a protein with the capacity to stimulate bone and cartilage growth in vitro. Its gene sequence identified it as an alternatively spliced human homolog of the Drosophila dorsal-ventral patterning tolloid gene and suggested that it activates transforming growth factor-beta-like molecules by proteolytic cleavage. Its expression pattern and its recently identified activity as a procollagen C proteinase, however, suggest that it has a more general function in the early stages of embryogenesis. This view is strengthened by the previous observation of a third alternatively spliced isoform of the gene, called bone morphogenetic protein 1/His. We now show that the gene is expressed in three additional variants, leading to shorter and slightly modified C-termini. The three variants are preferentially expressed in placenta but show individual differences in their expression profiles in other soft tissues.
J Mol Med (Berl) 1998 Feb
PMID:Three alternatively spliced variants of the gene coding for the human bone morphogenetic protein-1. 950 Jun 80


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