共查询到20条相似文献,搜索用时 31 毫秒
1.
Jonathan C. Fox Judith L. Swain 《In vitro cellular & developmental biology. Animal》1993,29(3):228-230
Summary Fibroblast growth factors (FGFs) are potent inhibitors of myogenic differentiation. The recent observation that the endogenous
expression of acidic and basic FGF by myogenic cells decreases coordinately with differentiation suggests a regulatory role
for these growth factors in myogenesis. Inasmuch as other proteins known to influence myogenesis (e.g., MyoD1 and myogenin)
activate their own expression as well as the expression of other members of their family, we hypothesized that the FGFs might
be capable of similar autoregulation. We examined the effect of exogenously supplied FGF on the abundance of the mRNAs encoding
acidic and basic FGF in Sol 8 myoblasts, and demonstrate that either acidic or basic FGF stimulate, through paracrine mechanisms,
the accumulation of the mRNAs encoding both of these FGFs. Thus FGFs can auto- and transregulate their own expression in a
manner analogous to that observed for the myogenic determination proteins. In addition, similar to that previously observed
for MyoD1, both acidic and basic FGF suppress myogenin expression in myoblasts. These results suggest two mechanisms whereby
endogenously produced FGFs participate in the maintenance of the undifferentiated state of myogenic cells. These data provide
support for paracrine, and suggest potential autocrine, roles for FGFs in the regulation of myogenic differentiation. 相似文献
2.
Acidic fibroblast growth factor (FGF) from bovine brain: amino-terminal sequence and comparison with basic FGF. 总被引:14,自引:2,他引:12
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Acidic fibroblast growth factor (FGF) from bovine brain has been isolated by a combination of salt precipitation, ion-exchange chromatography, heparin-Sepharose affinity chromatography and reverse phase h.p.l.c. The amino acid composition of the mitogen is indistinguishable from that of acidic FGF previously purified. The amino-terminal sequence of acidic FGF was established as Phe-Asn-Leu- Pro-Gly-Asn-Tyr-Lys-Pro-Lys-Leu-X-Tyr-X-Ser-Asn-Gly-X-Tyr-Phe-Leu-Arg-Il e-Leu-Pro-Asp-Gly. Acidic FGF is structurally different from basic FGF as judged by mol. wt., amino acid composition and sequence. In vitro biological comparison of the two growth factors indicates that acidic and basic FGFs possess the same intrinsic activities to stimulate the proliferation of aorta, vein or capillary endothelial cells and adrenal cortex cells, but acidic FGF is 30-100 times less potent, depending on the cell type. 相似文献
3.
4.
Abstract: Fibroblast growth factors (FGFs) are not only mitogens, but they also promote the differentiation of various cell types. For instance, basic FGF (bFGF) provides a critical trophic support for hippocampal neurons in culture. To elicit their biological effects, FGFs interact with high-affinity receptors that are transmembrane proteins with a cytoplasmic portion containing a tyrosine kinase activity. The tyrosine phosphorylation pattern was examined in primary cultures of hippocampal neurons derived from rat embryos. In these cultures grown for 3 days in the absence of serum, the addition of bFGF causes a rapid increase of tyrosine phosphorylation for various proteins with an optimal level after 5 min of bFGF exposure. Concomitantly, bFGF activates mitogen-activated protein kinase (MAP kinase) activity measured with a selective MAP kinase peptide. The activity increased rapidly after the addition of bFGF and remained elevated even when cultures were treated for 1 h with bFGF. Both acidic and basic FGF were able to enhance protein tyrosine phosphorylation and MAP kinase activity, whereas nerve growth factor and epidermal growth factor did not elicit any of these responses. These data indicate that some of the transduction signals (i.e., tyrosine phosphorylation and activation of MAP kinase) that have been described for the proliferative effect of FGFs are also involved when FGFs act as trophic factors for postmitotic neurons in culture. 相似文献
5.
《Progress in growth factor research》1992,4(2):107-120
Growth factors play a key role in cellular communication, a necessary step for the development of pluricellular organisms. The fibroblast growth factors (FGF) are among these polypeptides and have seven known members: FGF 1 to FGF 7 which are also known as acidic FGF, basic FGF, translation products of oncogenes hst, int 2, FGF 5, FGF 6 and FGF 7 or keratinocyte growth factor (KGF) respectively[1]. 2 The best known and the most abundant in normal adult tissues are acidic and basic FGFs, or FGF 1 and 2 respectively, which have been subjected to extensive studies both in vitro and in vivo. These two factors have almost ubiquitous distribution and a wide spectrum of biological activity including action on cellular proliferation and differentiation, as well as neurotrophic and angiogenic properties[1]. These different activities are induced by triggering specific receptors present at the surface of the target cell. Following this interaction, the FGF-receptor complexes are internalized and activate intracellular pathways. An important effort of investigations has been produced to characterize these receptors and intracellular pathways. It is the purpose of this review to present this work which will focus on FGFs 1 and 2. The existence of two classes of interactions has been reported as early as 1987 [52,53,54] suggesting the presence of high and low affinity receptors for FGFs. 相似文献
6.
Laurence W. Haynes 《Molecular neurobiology》1988,2(4):263-289
Nearly thirty growth and trophic factors that have been purified from mammalian tissues in the last 15 yr have been found to share chemical identity. The results of their chemical purification and molecular cloning show that they are two distinct polypeptides (Mr 17,400 and 18,400), each of which gives rise to families of smaller size peptides. These peptides share a common affinity for heparin. In view of this property, a common nomenclature for the two principle peptide growth factors (heparin-binding growth factor classes 1 and 2; HBGF-1 and -2) has been proposed. However, the names acidic and basic Fibroblast Growth Factors (aFGF,bFGF), which were applied to them originally to describe their mitogenic activity, are more commonly in use and will therefore be adopted in this review. Brain tissue is one of the richest sources of FGFs. It has been used as a starting point for their chemical purification and to prepare genomic libraries for molecular cloning of the aFGF and bFGF genes. There is increasing evidence that these growth factors, expressed in neurons and glia throughout the mammalian nervous system, are implicated in neuronal cell proliferation, differentiation, and histogenesis. FGFs have a strong affinity not only for heparin, but also for the related heparan sulphate proteoglycans that are abundant in neural tissues. This fact provides a clue to the importance of tissue-associated proteoglycans in mediating the release, sequestration, and activation of FGFs and the modulation of their receptor binding and bioactivity. The relevance of FGFs to neural development and their mechanisms of action in neurons will be considered in light of the existing literature describing their biological properties and activity in mesodermal cell types. Evidence is reviewed showing that FGFs have in vivo biological activity, ameliorating the degeneration of central and peripheral neurons after axotomy. The presence and implications of high levels of FGFs in adult mammalian brain provides a direction for future research into neural regeneration. The bioactivity of FGFs in neural tissue may not depend on the regulation of their expression per se, but on the subregional modification of their interaction with proteoglycans. 相似文献
7.
Endothelial cell growth factors in embryonic and adult chick brain are related to human acidic fibroblast growth factor. 总被引:4,自引:0,他引:4
We have investigated the nature of endothelial cell growth factors in 14-day embryonic and adult chick brain extracts. Mitogenic activity was isolated by a combination of cation-exchange, heparin-Sepharose affinity, and reverse-phase HPLC. Two major mitogenic fractions eluted from heparin-Sepharose at 0.8-1.3 M and 1.5-2 M. Biologically active proteins eluting at 0.8-1.3 M NaCl, after purification to homogeneity from embryonic and adult brain, were found to possess the same amino-terminal sequence as human acidic fibroblast growth factor (aFGF). The notion that the isolated mitogens represent chick aFGF is further supported by the findings that their affinity for heparin and their retention behavior in highly resolutive HPLC are indistinguishable from those of genuine aFGF. Mitogenic activities eluting at 1.5-2 M NaCl were also present in embryonic and adult brain, but in quantities insufficient for preliminary characterization. The high specific mitogenic activity for endothelial cells, high affinity for heparin and cross-reactivity with antibodies against bovine basic FGF (bFGF) suggest a relationship of those materials with basic FGF. Our data also suggest that the sequence of aFGF is highly conserved among vertebrates. While angiogenesis occurs predominantly in the embryonic brain, the absence of notable differences in the contents of the potent angiogenic factors aFGF and bFGF in embryonic versus adult chick brain is interesting. 相似文献
8.
Wu X Kamei K Sato H Sato SI Takano R Ichida M Mori H Hara S 《Protein expression and purification》2001,21(1):192-200
A hybrid of Autographa californica nuclear polyhedrosis virus and Bombyx mori nuclear polyhedrosis virus, which is infectious to both Spodoptera frugiperda and Bombyx mori, was prepared in our previous study. Two recombinant hybrid baculoviruses, carrying cDNAs of human acidic and basic fibroblast growth factors, respectively, were successfully constructed in this study, for the large-scale production of human aFGF and bFGF using silkworm as host. These recombinant viruses were used to inoculate silkworm larvae. After the infection, the recombinant proteins were not found in the hemolymph. Such nonsecretion from cells has also been observed in the established insect cell lines, Sf21 and Tn-5. Tissue distribution analysis indicated that the expressed products were mainly located in fat body and the production of the recombinant aFGF and bFGF was maximal at around 80 h postinfection. Therefore, silkworm larvae infected with recombinant viruses were dissected and fat bodies were collected for the purification of recombinant aFGF and bFGF. The expression levels in both cases were estimated to be as high as approximately 600-700 microg per larva. Furthermore, the recombinant proteins were characterized and their biological activities were evaluated by in vitro bioassay using cell culture. 相似文献
9.
P L Ho M R Carpenter L B Smillie A G Gambarini 《Biochemical and biophysical research communications》1990,170(2):769-774
Acidic and basic fibroblast growth factors (FGFs) are proteins of 16-18 kDa. Other forms of 25-30 kDa related to this growth factor family have recently been described. All these components bind tightly to heparin-Sepharose, a property that allows the purification of several FGF-related proteins. During the purification of acidic and basic FGFs from bovine pituitary glands, we detected the presence of 28-30 kDa components that are immunoreactive against anti-basic FGF antisera. However, microsequencing analysis revealed that the 28-30 kDa components are lysosomal proteases that co-elute with basic FGF from heparin-Sepharose columns. The involvement of these proteases in the etiology of microheterogenous forms of FGFs and/or release of FGFs from the extracellular matrix is discussed. 相似文献
10.
Processing, secretion, and biological properties of a novel growth factor of the fibroblast growth factor family with oncogenic potential. 总被引:21,自引:6,他引:15
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P Delli-Bovi A M Curatola K M Newman Y Sato D Moscatelli R M Hewick D B Rifkin C Basilico 《Molecular and cellular biology》1988,8(7):2933-2941
We recently reported that the protein encoded in a novel human oncogene isolated from Kaposi sarcoma DNA was a growth factor with significant homology to basic and acidic fibroblast growth factors (FGFs). To study the properties of this growth factor (referred to as K-FGF) and the mechanism by which the K-fgf oncogene transforms cells, we have studied the production and processing of K-FGF in COS-1 cells transfected with a plasmid encoding the K-fgf cDNA. The results show that, unlike basic and acidic FGFs, the K-FGF protein is cleaved after a signal peptide, glycosylated, and efficiently secreted as a mature protein of 176 or 175 amino acids. Inhibition of glycosylation impaired secretion, and the stability of the secreted K-FGF was greatly enhanced by the presence of heparin in the cultured medium. We have used the conditioned medium from transfected COS-1 cells to test K-FGF biological activity. Similar to basic FGF, the K-FGF protein was mitogenic for fibroblasts and endothelial cells and induced the growth of NIH 3T3 mouse cells in serum-free medium. Accordingly, K-fgf-transformed NIH 3T3 cells grew in serum-free medium, consistent with an autocrine mechanism of growth. We have also expressed the protein encoded in the K-fgf protooncogene in COS-1 cells, and it was indistinguishable in its molecular weight, glycosylation, secretion, and biological activity from K-FGF. Taken together, these results suggest that the mechanism of activation of this oncogene is due to overexpression rather than to mutations in the coding sequences. 相似文献
11.
Platelet-derived growth factors and fibroblast growth factors are mitogens for rat Schwann cells 总被引:11,自引:5,他引:6
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Rat sciatic nerve Schwann cells in culture respond to a limited range of mitogens, including glial growth factor, transforming growth factors beta-1 and beta-2 (TGF-beta 1, TGF-beta 2), some cell membrane-associated factors, and to agents such as cholera toxin and forskolin which raise intracellular levels of cAMP. These responses require the presence of FCS, which exhibits little or no mitogenic activity in the absence of other factors. However, we recently found that forskolin greatly potentiates the mitogenic signal from TGFs-beta 1 and beta 2, raising the possibility that cAMP might couple other factors to mitogenesis. We have therefore screened a range of candidate mitogens using DNA synthesis assays. Other than TGFs-beta and glial growth factor, none of the factors tested were mitogenic in the presence of 10% serum alone. With the addition of forskolin, however, porcine PDGF, human PDGF, acidic and basic FGF were potent mitogens for rat Schwann cells, stimulating DNA synthesis and increasing cell number. Cholera toxin and dibutyrylcyclicAMP, but not 1,9-dideoxyforskolin, can substitute for forskolin indicating that the mitogenic effect is mediated via adenylyl cyclase activation. Porcine PDGF gave half-maximal stimulation at 15 pM, and human PGDF an equivalent response at 1 nM. Basic FGF was half maximal at 5 pM, acidic FGF at 1 nM. The recognition of PDGFs and FGFs as mitogens for Schwann cells has many implications for the study of Schwann cell proliferation in the development and regeneration of nerves, and in Schwann cell tumorigenesis. 相似文献
12.
Nur-E-Kamal A Ahmed I Kamal J Babu AN Schindler M Meiners S 《Molecular and cellular biochemistry》2008,309(1-2):157-166
Activation of fibroblast growth factor receptors (FGFRs) requires the formation of a ternary complex between fibroblast growth
factors (FGFs), FGFRs, and heparan sulfate proteoglycans, which are all located on the cell surface and the basement membrane
(BM)/extracellular matrix (ECM). Heparan sulfate proteoglycans appear to stabilize FGFs by inhibiting the rapid degradation
of FGFs normally observed in solution. Because of the pivotal role of FGFs in proliferative and developmental pathways, a
number of recent studies have attempted to engineer microenvironments to stabilize growth factors for use in applications
in tissue culture and regenerative medicine. In this communication, we demonstrate that covalent linkage of FGF-2 to nanofibrillar
surfaces (defined as covalently bound FGF-2) composed of a network of polyamide nanofibers resulted in the maintenance of
the biological efficacy of FGF-2 when stored dry for at least 6 months at 25°C or 4°C. Moreover, covalently bound FGF-2 was
more potent than FGF-2 in solution when measured in cellular assays of proliferation and viability using a variety of cell
types. Covalently bound FGF-2 also strongly activated FGFR, extracellular signal-regulated kinase (ERK1/2), and c-fos. Hence
cell-signaling molecules can be incorporated into a synthetic nanofibrillar surface, providing a novel means to enhance their
stability and biological activity. 相似文献
13.
J B Takahashi M Hoshimaru M Jaye H Kikuchi M Hatanaka 《Biochemical and biophysical research communications》1992,189(1):398-405
Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo. 相似文献
14.
J. A. Andrades J. A. Santamaría L. T. Wu F. L. Hall M. E. Nimni J. Becerra 《Protoplasma》2001,218(1-2):95-103
Summary Basic fibroblast growth factor (bFGF) is a potent in vitro mitogen for capillary endothelial cells, stimulates angiogenesis in vivo, and may participate in tissue repair. Basic FGF is found in abundance in tissues such as brain, kidney, and cartilage. This study reports the expression, purification, and renaturation of a biologically active human basic fibroblast growth factor fusion protein (hbFGF-Fl) fromEscherichia coli. A prokaryotic expression vector was engineered to produce a tripartite fusion protein consisting of a purification tag, a protease-sensitive linker and collagen binding domain, and a cDNA sequence encoding the active fragment of hbFGF. The expressed hbFGF-F1 and hbFGF-F2 (it contains the collagen binding domain), located in inclusion bodies, were solubilized with 6 M guanidine-HCl and renatured by a glutathione redox system and protracted dialysis under various experimental conditions. The purification of the recombinant proteins was achieved by binding the His-tag of the fusion protein on a nickel-nitrilotriacetic acid metal chelate column. The biological activity of the recombinant growth factor was demonstrated by its ability to stimulate proliferation of human vein endothelial cells, monitored by [3H]thymidine incorporation, where commercial recombinant human bFGF (rhbFGF) served as a positive control. Purified rhbFGF-F1 and rhbFGF-F2 constructs exhibited proliferative activity comparable to commercial rhbFGF. The high-affinity binding was demonstrated by the binding of [3H]collagen to the rhbFGF-F2 protein immobilized on a Ni-nitrilotriacetic acid column. The rhbFGF-F2 fusion protein bound to collagen-coated surfaces with high affinity. Taken together, these results demonstrate that biologically active rhbFGF fusion proteins can be recovered from transformed bacteria by oxidative refolding; thus, providing a means for their high-yield production, purification, and renaturation from microorganisms. Furthermore, we demonstrate that the auxiliary collagen binding domain effectively targets the recombinant growth factor to type 1 collagen. These studies advance the technology necessary to generate large quantities of targeted bFGF fusion proteins for specific biomedical applications. 相似文献
15.
Yushi Matuo Nozomu Nishi Yasuyoshi Muguruma Yoshino Yoshitake Yoshishige Masuda Katsuzo Nishikawa Fumio Wada 《In vitro cellular & developmental biology. Plant》1988,24(5):477-480
Summary The potential usefulness of a zwitterionic detergent, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS),
in the stabilization of acidic and basic fibroblast growth factors (FGFs) was examined. Among several detergents, CHAPS was
found to be not only non-cytotoxic but also most useful in handing the diluted preparations of FGFs. The advantages are as
follows: 1) at lower concentrations than 0.01% CHAPS did not affect growth factor activity of calf serum (CS) and the growth
rate of BLAB/c 3T3 cells. The primary culture of rat prostate epithelium and colony formation of NRK-49F cells were hardly
influenced by CHAPS lower than 0.003%; 2) the loss of FGFs that usually occurs due to their adherence to the surface of storage
containers was effectively prevented by inclusion of 0.1% CHAPS; 3) the recovery of FGFs after storage or dialysis was significantly
enhanced by inclusion of 0.1% CHAPS; 4) CHAPS at lower concentrations than 0.1% does not interfere with amino acid analysis,
except that Thr may be misled only when the ratio of protein/CHAPS is low; 5) amino acid sequence analysis was hardly disturbed
by CHAPS up to 0.5%. These results indicate that CHAPS is useful as a stabilizing agent for various kinds of polypeptides
capable of showing biological activity at a low concentration.
Editor's statement Polypeptide growth factors and hormones, especially heparin-binding growth factors (FGF), are notoriously
troublesome to handle in purified form at extremely low concentrations. This report demonstrates an interesting solution to
this problem. 相似文献
16.
Stephen R. Campion Elizabeth Elsasser Roger Chung 《Protein expression and purification》1997,10(3):331-339
AnEscherichia coliexpression system that exploits the bacterial alkaline phosphatase (PhoA) signal sequence to translocate recombinant human epidermal growth factor (hEGF) to the periplasm was used to evaluate how changes in the composition and sequence of amino acids near the PhoA–hEGF junction influence the periplasmic accumulation of recombinant protein. A series of chimeric structural genes was generated byin vitroreplacement of hEGF sequence with analogous segments from the EGF-like domain of human heregulin (HRG), significantly altering the electrostatic character of the amino-terminal region of the mature protein. Quantitation of HRG/EGF protein inE. coliperiplasmic extracts, by RP-HPLC, showed a fourfold decrease after one of two acidic residues located in the amino-terminal region of the mature hEGF, near the PhoA junction, was replaced. An additional threefold decrease was observed when the second acidic residue was replaced with a positively charged lysine. Further extension of the amino-terminal HRG sequence, beyond the first six residues, resulted in net neutralization of a more distant EGF acidic residue with no additional effect on protein yield. The importance of having a negatively charged group in the amino-terminal region of the mature protein was confirmed when insertion of an aspartic acid near the amino-terminus of two poorly expressed hybrid protein sequences resulted in a five- to eightfold increase in their recovery from the periplasm. This study demonstrates the importance of having negatively charged residues near the fusion junction of recombinant proteins expressed inE. coliusing the PhoA signal sequence for protein export. 相似文献
17.
The production of hantavirus Puumala nucleocapsid (N) protein for potential applications as a vaccine and for diagnostic purposes was investigated with Saccharomyces cerevisiae as a recombinant host. The N protein gene and the hexahistidine tagged N (h-N) protein gene were expressed intracellular from a 2-microm plasmid vectors under the control of a fused galactose inducible GAL10-PYK promoter. For monitoring the recombinant gene expression, a h-N and a GFP fusion protein was used. Different cultivation strategies and growth media compositions were tested in shake flasks and a 5 l bioreactor. When using defined YNB growth medium, we found the biomass yield to be unsatisfactorily low. Higher concentrated YNB medium, promoted cell growth but showed a pronounced inhibitory effect on heterologous gene expression. This phenomenon could not be attributed to plasmid losses, as we could demonstrate high stability of the vector under the applied cultivation conditions. Supplementation of YNB medium with extracts of plant origin resulted in increased biomass yields with concomitant high expression levels of the recombinant gene. The modified medium was used for fed-batch cultivations where basic metabolic features as well as growth parameters were determined in addition to recombinant gene expression. The maximal volumetric yield of N protein was 316 mg l(-1), the respective yield of h-N protein was 284 mg l(-1). Our study provides a basis for large-scale production of hantavirus vaccines, which satisfies economic efficiency as well as biosafety regulations for human applications. 相似文献
18.
We have developed a family of cloning vectors that direct expression of fusion proteins that mimic aggregated immunoglobulin (IgG) (AIG) and immune complex function with respect to their interactions with FcgammaR and that allow for the inclusion and targeting of a second protein domain to cells expressing FcgammaR. This was accomplished by expressing multiple linear copies of the hinge and CH2 domains (HCH2) of human IgG(1) fused to the framework region of human IgG(1). Convenient restriction sites allow for the facile introduction of additional amino-terminal domains. The resulting molecule is tripartite. The carboxyl-IgG(1) framework domain provides stability and permits dimerization, and the intervening polymer provides increased effector function and targeting to FcgammaR while the amino-terminal domain can deliver an additional signal to cells expressing FcgammaR. To demonstrate the utility of the vectors, the extracellular domain of human CD8alpha was expressed as a HCH2 polymer fusion protein. The fusion proteins were secreted in useful amounts from polyclonal cell lines established in Sf9 cells following transfection and selection with G418. The biological activity of the recombinant CD8alpha-HCH2 polymers was determined and compared to those of AIG and an anti-CD16 monoclonal antibody using an in vitro assay. The activity of the fusion proteins positively correlates to the number of HCH2 units. The largest polymer tested was severalfold more potent than AIG at similar concentrations. The HCH2 polymers described here represent a new strategy in the design of recombinant proteins for the therapeutic targeting of FcgammaR in autoimmune disorders. 相似文献
19.
Fibroblast growth factors (FGF) in human myometrium and uterine leiomyomas in various stages of tumour growth 总被引:1,自引:0,他引:1
We previously described that the growth of human uterine leiomyomas was associated with a significant remodelling of the extracellular matrix of these tumours. Significant weight-related increase of collagen and heparan sulphate contents was detected. The latter was known as a component, which bound some peptide growth factors, mainly FGFs, therefore it was decided to evaluate the amounts of acidic FGF (aFGF) and basic FGF (bFGF) in human myometrium and in leiomyomas of various weight and FGF-binding to tissue components. It was found that myometrium and uterine leiomyomas contain picogram amount of aFGF and nanogram amounts of bFGF. No free aFGF was found. Slight amounts of free bFGF were detected both in myometrium and in the tumours. The aFGF and most of bFGF existed in a form of complex with a high molecular component(s). These complexes were very stable and they did not dissociate in denaturation conditions. In comparison to myometrium the tumours contained several times more FGFs and their amounts distinctly increased during the tumour growth. The expression of FGF-receptor I (FGF RI) in the tumours was more distinct in comparison to myometrium. The extracts from myometrium did not bind exogenous 125I-bFGF. In contrast to that the tumours of different weights contained at least two high molecular weight FGF-binding components. One of them (150 kDa) corresponded to FGF-receptor. The other one (190-200 kDa) might be a heparan sulphate-proteoglycan. It seems that aFGF and bFGF play an important role in transformation of normal myometrium into leiomyoma and further growth of this tumour. The action of FGFs on tumour cells enhances biosynthesis of collagen and sulphated glycosaminoglycans, especially heparan sulphate which binds FGFs in the vicinity of cells and facilitates their interaction with membrane receptors. The effect of these processes may be further stimulation of tumour growth and remodelling of tumour extracellular matrix. 相似文献
20.
Recently, the partial structural characterization of a novel bovine brain protein was reported (1). Because of its mitogenic activity for vascular endothelial cells and its ability to strongly bind heparin it was termed heparin-binding brain mitogen (HBBM). Although HBBM shares these properties with members of the fibroblast growth factor (FGF) family of growth factors, its aminoterminal sequence is not homologous to that of the FGFs. Now, we report the isolation and partial structural characterization of HBBMs from human, rat and chick brain. Proteins were isolated by tissue extraction at pH 4.5, ammonium sulfate precipitation, cation exchange chromatography, heparin-Sepharose affinity chromatography and reverse-phase HPLC. The amino-terminal sequences of the HBBMs from human, bovine and rat brain are identical, whereas that of chick HBBM reveals a single amino acid substitution. The high sequence homology among the HBBMs from different species suggests an important biological role of the protein.Special issue dedicated to Dr. Sidney Udenfriend. 相似文献