| 1. |
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| 2. |
- Annerén, Cecilia, et al.
(författare)
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Role of the Bsk/lyk non-receptor tyrosine kinase for the control of growth and hormone production in RINm5F cells
- 2000
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 17, s. 233-247
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Tidskriftsartikel (refereegranskat)abstract
- Bsk/Iyk, a murine non-receptor-tyrosine kinase which is expressed in fetal and adult islet of Langerhans was previously found to decrease NIH3T3 cell proliferation when expressed as a Y497/504F-mutant. We presently wanted to determine the effects of Bsk/Iyk on the proliferation of insulin producing cells. Cells expressing Bsk/IykY497/504F and Bsk/IykY504F display a decreased proliferation rate and express higher levels of the cell cycle inhibitor p27/Kip1 compared to control cells. These mutants also conferred diminished cell viability in response to INF-gamma and IL-1beta and contain higher levels of glucagon mRNA. Wild-type Bsk/Iyk is mainly localized at the plasma membrane whereas mutant Bsk/Iyk can enter the nucleus. In vitro kinase reactions using an exogenous substrate indicate a complicated mode of regulation of kinase activity by Y497 and Y504 with the latter being homologous to Y527 in pp60c-Src. These findings suggest that Bsk/Iyk might play a role in inhibiting cell proliferation, transducing cytokine-induced cytotoxicity and regulating hormone production of endocrine pancreatic cells.
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| 3. |
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| 4. |
- Demoulin, Jean-Baptiste, et al.
(författare)
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The gene expression profile of PDGF-treated neural stem cells corresponds to partially differentiated neurons and glia
- 2006
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 24:3, s. 184-196
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that platelet-derived growth factor AA (PDGF-AA) stimulates the expansion of neuronal progenitors from neural stem cells, but is unable to replace fibroblast-growth factor 2 (FGF-2) as a stem cell mitogen. In the present study, we compared gene expression in neural stem cells that were grown in the presence of FGF-2 and in cells cultured with PDGF-AA or in the absence of growth factor, which induces differentiation. The genetic program elicited by PDGF-AA (156 significantly regulated genes) was not unique, but an intermediate between the ones of FGF-2-cultured stem cells and differentiated cells. These observations are compatible with the hypothesis that PDGF-AA induces a partial differentiation of neural stem cells, which retain the ability to proliferate, rather than acting solely as an instructing agent for neuronal differentiation. Finally, the transcriptional signature of stem cells grown with FGF-2 included a large number of genes over-expressed in gliomas and a core set of conserved genes periodically expressed during the eukaryote cell cycle.
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| 5. |
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| 6. |
- Eliasson, Pernilla, et al.
(författare)
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Myostatin in tendon maintenance and repair
- 2009
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 27:4, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.
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| 7. |
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| 8. |
- Hawinkels, Lukas J A C, et al.
(författare)
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Exploring anti-TGF-β therapies in cancer and fibrosis
- 2011
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 29:4, s. 140-152
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor-β (TGF-β) is a multifunctional cytokine, with important roles in maintaining tissue homeostasis. TGF-β signals via transmembrane serine/threonine kinase receptors and intracellular Smad transcriptional regulators. Perturbed TGF-β signaling has been implicated in a large variety of pathological conditions. Increased TGF-β levels have been found in patients with cancer, fibrosis, and systemic sclerosis, and were correlated with disease severity. In cancer, TGF-β mediates tumor invasion and metastasis by affecting both tumor cells and the tumor microenvironment including fibroblast activation and immune suppression. Furthermore, TGF-β is a strong stimulator of extracellular matrix deposition. On the basis of these observations, small molecule inhibitors of the TGF-β receptor kinases, neutralizing antibodies that interfere with ligand?receptor interactions, antisense oligonucleotides reducing TGF-β expression, and soluble receptor ectodomains that sequester TGF-β have been developed to intervene with excessive TGF-β signaling activity in the aforementioned disorders. Here, we review the current state of anti-TGF-β therapy in clinical trials.
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| 9. |
- Heldin, Carl-Henrik
(författare)
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Tony Pawson (1952-2013)
- 2014
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Ingår i: Growth Factors. - : Taylor & Francis. - 0897-7194 .- 1029-2292. ; 32:6, s. 174-175
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 10. |
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| 11. |
- Larsson, Karin, et al.
(författare)
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Increased levels of the cardiovascular disease risk biomarkers GDF15 and myostatin in patients with chronic lymphocytic leukemia
- 2021
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 38:3-4, s. 189-196
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Tidskriftsartikel (refereegranskat)abstract
- Individuals suffering from cancer, including hematological malignancies, are at increased risk of cardiovascular disease (CVD). Elevated levels of several biomarkers in blood are associated with an increased risk of CVD. The aim of this study was to investigate whether a subset of such CVD risk biomarkers was elevated in patients with untreated chronic lymphocytic leukemia (CLL). Blood plasma and serum from 139 CLL patients and 71 healthy age-matched controls were analyzed for 11 proposed CVD risk biomarkers. The CLL cohort displayed a more heterogeneous pattern of biomarker expression compared to controls. The majority, eight out of 11, analyzed CVD risk biomarkers differed significantly in concentrations between CLL patients and controls. Increased levels of the biomarkers GDF15 and myostatin have not previously been reported in CLL. Further prospective studies are warranted to investigate whether these biomarkers predict future cardiovascular events in patients with CLL.
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| 12. |
- Lavenius, Erik, et al.
(författare)
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Basic FGF and IGF-I promote differentiation of human SH-SY5Y neuroblastoma cells in culture
- 1994
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Ingår i: Growth Factors. - : Taylor & Francis. - 0897-7194 .- 1029-2292. ; 10:1, s. 29-39
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Tidskriftsartikel (refereegranskat)abstract
- Phorbolester-triggered differentiation of SH-SY5Y neuroblastoma cells requires serum and a prolonged activation of protein kinase C (PKC). Under serum-free conditions development of a mature phenotype requires phorbolester in combination with a member of either the insulin-like growth factor (IGF) or the platelet-derived growth factor family. Here we report that basic and acidic fibroblast growth factor (FGF) and epidermal growth factor, but not nerve growth factor, synergistically potentiate phorbolester-induced differentiation. Alone these factors induced a mitogenic response which varied in magnitude, with basic FGF and IGF-I being the two most potent mitogens. However, a combination of basic FGF and IGF-I induced differentiation as judged by morphology and the increase in growth associated protein (GAP-43) and neuropeptide tyrosine mRNA levels. In contrast to the phenotype obtained in the presence of phorbolester, bFGF and IGF-I-treated SH-SY5Y cells retained their capacity to proliferate. Finally, in these cells, the phosphorylation of the endogenous PKC substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), was slightly increased during several days, suggesting an involvement of PKC in the bFGF and IGF-I-induced differentiation.
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| 13. |
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| 14. |
- Malmsten, Martin, et al.
(författare)
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Antimicrobial peptides derived from growth factors
- 2007
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 25:1, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- Growth factors, comprising diverse protein and peptide families, are involved in a multitude of developmental processes, including embryogenesis, angiogenesis, and wound healing. Here we show that peptides derived from HB-EGF, amphiregulin, hepatocyte growth factor, PDGF-A and PDGF-B, as well as various FGFs are antimicrobial, demonstrating a previously unknown activity of growth factor-derived peptides. The peptides killed the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis, as well as the fungus Candida albicans. Several peptides were also active against the Gram-positive S. aureus. Electron microscopy analysis of peptide-treated bacteria, paired with analysis of peptide effects on liposomes, showed that the peptides exerted membrane-breaking effects similar to those seen after treatment with the “classical” human antimicrobial peptide LL-37. Furthermore, HB-EGF was antibacterial per se, and its epitope GKRKKKGKGLGKKRDPCLRKYK retained its activity in presence of physiological salt and plasma. No discernible hemolysis was noted for the growth factor-derived peptides. Besides providing novel templates for design of peptide-based antimicrobials, our findings demonstrate a previously undisclosed link between the family of growth factors and antimicrobial peptides, both of which are induced during tissue remodelling and repair.
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| 15. |
- Mehmet, Huseyin, et al.
(författare)
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Early signals in the mitogenic response of Swiss 3T3 cells : a comparative study of purified PDGF homodimers
- 1990
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Ingår i: Growth Factors. - : Taylor & Francis. - 0897-7194 .- 1029-2292. ; 3:2, s. 83-95
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor (PDGF) occurs as three dimeric isoforms, AA, BB, and AB. Two distinct receptor subunits, alpha and beta, have been identified which bind either all three isoforms of PDGF (alpha) or PDGF-BB only (beta). Here, we have compared the effect of purified PDGF homodimers on the early intracellular signaling events and mitogenesis in Swiss 3T3 cells, which possess equivalent numbers of the alpha and beta subunits. Both PDGF-AA and PDGF-BB stimulated receptor phosphorylation, inositol phosphate formation, activation of protein kinase C, calcium mobilization, EGF receptor transmodulation, sodium uptake, arachidonic acid release, cyclic AMP accumulation, and c-fos induction in a comparable, dose-dependent manner (half-maximal values for all these response were in the 2-10 ng/ml range for both homodimers). At high concentrations of PDGF (greater than 10 ng/ml), the BB homodimer effect on early membrane and cytosolic signals was 20-30% greater than PDGF-AA, reflecting the greater number of available binding sites for PDGF-BB. DNA synthesis studies indicated that PDGF-AA and PDGF-BB were potent mitogens for Swiss 3T3 cells, displaying identical dose-response effects. Moreover, the mitogenic activities of both homodimers were equally potentiated in the presence of insulin. These results indicate that both PDGF-AA and PDGF-BB stimulate the full complement of molecular responses required for the synergistic interactions mediating long-term mitogenesis. We conclude that alpha and beta receptor subunits do not differ in their ability to transduce PDGF-mediated signals leading to DNA synthesis in Swiss 3T3 cells.
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| 16. |
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| 17. |
- Miller, S J, et al.
(författare)
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A novel type of regulatory element is required for promoter-specific activity of the PDGF-B intronic enhancer region.
- 1998
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 16:2, s. 137-51
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Tidskriftsartikel (refereegranskat)abstract
- We have previously described a non-classical, promoter-specific enhancer for the human Platelet-Derived Growth Factor B (PDGF-B) gene. In JEG-3 choriocarcinoma cells the activity of the enhancer depends upon co-operation with a sequence (the Enhancer-Dependent cis Co-activator "EDC" element) within the promoter. The PDGF-B enhancer fails to activate heterologous promoters, indicating that promoter-specificity depends on an element within the enhancer that can recognise a target sequence within the promoter. Here we identify a sequence within the enhancer of the PDGF-B gene which directs activation of the PDGF-B promoter by distal cis-acting elements. This specifies the wild-type PDGF-B promoter as the target for the enhancer and has been designated the EDC specificity element (EDCse). The cell-type specific nature of this interaction is extended by the observation that the EDCse is also dispensable for enhancer activity in breast-cancer cells (ZR-75). Concomitant to this observation, JEG-3 and ZR-75 cells differ in the binding of nuclear factors to the EDCse. We discuss the relevance of the EDC/EDCse system in regulation of gene expression.
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| 18. |
- Nayeri, Fariba, et al.
(författare)
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An in vitro model for assessment of the biological activity of hepatocyte growth factor
- 2007
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 25:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is a multifunctional growth factor with potent wound-healing properties that functions in the healing of chronic injuries. However, there may be a loss of HGF activity in certain chronic cases; this might be indicated by the presence of high amounts of HGF in body fluids and by the elevated expression of the HGF receptor in tissue biopsies. In such cases, a reliable means of assessing the activity of endogenous HGF would be valuable in allowing clinicians to decide if treatment with HGF would be useful. In this study, we developed an in vitro wound assay that used a mouse skin epithelial cell line to evaluate the biological activity of HGF. We showed that HGF accelerated the motility of the epithelial cells in a dose-dependent fashion with high sensitivity and specificity. This in vitro assay might be used to determine the activity of both endogenous and recombinant HGF.
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| 19. |
- Nayeri, Fariba, 1958-, et al.
(författare)
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Clinical impact of real-time evaluation of the biological activity and degradation of hepatocyte growth factor
- 2008
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 26:3, s. 163-171
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocyte growth factor (HGF) is essential for injury repair. Despite high HGF levels in chronic ulcers, up-regulation of HGF receptor in ulcer tissue and decreased biological activity of HGF in ulcer secretions have been observed. With a surface plasmon resonance-based method, we assessed the binding of HGF to antibodies, receptors, and the basement membrane and identified binding interactions that are indispensable for the biological activity of HGF. Recombinant HGF (rHGF) lots were tested for activity, structural integrity, and degradation, and the results were verified in an in vitro model of cell injury. Biologically active rHGF, as well as plasma from healthy volunteers, bound to heparan sulphate proteoglycan (HSPG) and to anti-HGF antibodies. Decreased binding to HSPG was the first event in rHGF degradation. This study established the feasibility of identifying patients with chronic inflammation who need exogenous HGF and of using ligand-binding assessment to evaluate rHGF lots for biological activity.
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| 20. |
- Oberg, C, et al.
(författare)
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Expression of protein tyrosine kinases in islet cells : possible role of the Flk-1 receptor for beta-cell maturation from duct cells.
- 1994
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 10:2, s. 115-26
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the expression of genes of importance for beta-cell replication and the production of insulin, single-stranded cDNAs from different preparations of insulin producing cells were used as template for the polymerase chain reaction (PCR) using primers specific for protein tyrosine kinases (PTKs). In RINm5F cells, as well as in fetal rat islets, the receptor PTK fetal liver kinase-1 (Flk-1) was expressed among other receptor and cytoplasmic tyrosine kinases. To elucidate the putative effects of stimulation of the Flk-1 receptor, fetal rat islet-like structures were cultured in the presence of the ligand for this receptor, vascular endothelial growth factor (VEGF). VEGF was found to stimulate both the insulin content/islet DNA ratio and the accumulation of insulin in the culture medium without affecting the rates of beta-cell replication. To investigate the localization of expression of the Flk-1 receptor in the pancreas, serial sections of fetal pancreata were immunostained for Flk-1 and insulin. Expression of Flk-1 was detected in endothelial-like cells and cells lining pancreatic ducts. The latter are considered to contain precursor cells for the endocrine pancreas. In conclusion, specific protein tyrosine kinases are expressed in islet cells, and are presumably participating in the regulation of islet function. Specifically, the receptor PTK Flk-1 may play a role of beta-cell maturation from pancreatic duct cells.
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| 21. |
- Risau, W, et al.
(författare)
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Platelet-derived growth factor is angiogenic in vivo
- 1992
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 7:4, s. 261-266
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- PDGF receptors have recently been found to be expressed in microvascular endothelium in vivo under circumstances of endothelial cell activation and angiogenesis suggesting that PDGF may have a direct effect on endothelial cells. We have tested the angiogenic activity of PDGF-AA and -BB homodimers in the chick chorioallantoic membrane in vivo. PDGF-BB was found to consistently induce an angiogenic response whereas PDGF-AA was less active. Morphological analyses revealed that there was little inflammation associated with this response but an increase in vessel density suggested a direct effect of PDGF on embryonic chorioallantoic endothelial cells. In vitro, PDGF-BB was found to be more potent than PDGF-AA in stimulating the chemotaxis of rat brain capillary endothelial cells. This is consistent with a direct effect of PDGF on endothelial cells. Thus, this novel angiogenic activity of PDGF has implications for several developmental and pathological events in which PDGF, particularly the B-chain, is expressed.
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| 22. |
- Smits, Anja, et al.
(författare)
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Rat brain capillary endothelial cells express functional PDGF B-type receptors
- 1989
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 2:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Immunohistochemical staining revealed the presence of platelet-derived growth factor (PDGF) B-type receptors on capillaries of normal rat brain. Furthermore, capillary endothelial cells isolated from rat brain and grown in tissue culture bound [125I]PDGF-BB but not [125I]PDGF-AA, suggesting that they expressed B-type, but not A-type, PDGF receptors. PDGF-BB and PDGF-AB, but not PDGF-AA, also stimulated incorporation of [3H]thymidine into these cells. Thus, rat brain capillary endothelial cells have functional B-type receptors, and thereby differ from endothelial cells derived from large blood vessels, that do not express PDGF receptors. Our data suggest a possible role for PDGF-BB as an angiogenic factor.
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| 23. |
- Stojanovic, Ivana, et al.
(författare)
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Macrophage migration inhibitory factor (MIF) enhances palmitic acid- and glucose-induced murine beta cell dysfunction and destruction in vitro.
- 2012
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 30:6, s. 385-393
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Tidskriftsartikel (refereegranskat)abstract
- Although several reports suggest a potentially deleterious role of macrophage migration inhibitory factor (MIF) in type 2 diabetes (T2D) pathology, it is still unclear how this pro-inflammatory cytokine acts on pancreatic beta cells. The aim of the present study was to evaluate MIF effects on murine beta cells in the in vitro settings mimicking T2D-associated conditions. Results indicate that recombinant MIF further increased apoptosis of pancreatic islets or MIN6 cells upon exposure to palmitic acid or glucose. This was accompanied by upregulation of several pro-apoptotic molecules. Furthermore, MIF potentiated nutrient-induced islet cell dysfunction, as revealed by lower glucose oxidation rate, ATP content, and depolarized mitochondrial membrane. The final outcome was potentiation of mitochondrial apoptotic pathway. The observed upregulation of nutrient-induced islet cell dysfunction and apoptosis by MIF implicates that silencing MIF may be beneficial for maintaining integrity of endocrine pancreas in obesity-associated T2D.
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| 24. |
- Suutre, Siim, et al.
(författare)
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Bone tissue content of TGF-2 changes with time in human heterotopic ossification after total hip arthroplasty
- 2009
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Ingår i: Growth Factors. - : Taylor & Francis. - 0897-7194 .- 1029-2292. ; 27:2, s. 114-120
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor beta isoforms (TGF-1, TGF-2, and TGF-3) most likely play a role in bone physiology, but little is known about their relative importance in normal as well as in heterotopic bone. This study focused on possible differences in the localization and relative content of different TGF beta isoforms in heterotopic ossifications (HO) by comparing HOs, which have developed less than 17 months (immature HOs) with those developed 3-9 years (mature HOs). The HOs were harvested after total hip arthroplasty (THA) during revision surgery. The HO samples were decalcified, embedded in paraffin and sectioned. Azan staining was used to evaluate histological structure of the ossifications and immunohistochemical analysis was performed to estimate the localization of three TGF beta isoforms in the HOs. Comparison of different TGF beta isoforms in the immature and the mature ossifications showed that the content of TGF-2 was decreased by almost three times in the mature HO as compared to the immature HO (p=0.0064). The proportions of other isoforms in HOs did not differ significantly. This study shows that the relative importance of TGF betas change with HO development.
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| 25. |
- Tarkkonen, Kati, et al.
(författare)
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Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells
- 2010
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 28:4, s. 256-267
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Tidskriftsartikel (refereegranskat)abstract
- Expression of fibroblast growth factor 8 (FGF-8) is increased in several forms of hormonal cancer. It was previously shown to regulate expression of thrombospondin 1 (TSP-1), an inhibitor of angiogencsis, in S115 breast cancer cells. Here, we studied the FGF-8-activated signalling pathways mediating TSP-1 repression in S115 cells and in non-tumorigenic MCF10A cells. Inhibition of FGF receptors or of MEK1/2 and PI3K with specific inhibitors (PD173074, U0126 or LY294002, respectively) restored TSP-1 mRNA expression in the presence of FGF-8 in S115 cells. Furthermore, U0126 and LY294002 increased TSP-1 mRNA expression in S115 cells over-expressing FGF-8. In MCF10A cells, FGF-8 treatment also decreased TSP-1 expression and the effect was dependent on active MEK1/2. In conclusion, FGF-8 suppresses TSP-1 expression through two independent pathways, MEK1/2 and PI3K. Repression of Tsp-1 may be an important mechanism involved in induction of an angiogenic phenotype and growth of FGF-8-expressing breast cancer.
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| 26. |
- Ullerås, Erik, et al.
(författare)
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The sequential activation and repression of the human PDGF-B gene during chronic hypoxia reveals antagonistic roles for the depletion of oxygen and glucose
- 2001
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 19:4, s. 233-245
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxia and glucose deprivation, are important during many physiological and pathological processes. Cells respond to these stimuli by activating genes involved in the regulation of metabolism and angiogenesis. Platelet derived growth factor-B (PDGF-B) is involved in the regulation of angiogenesis and tumour progression and is induced by hypoxia. Most known hypoxia-induced genes are activated by the hypoxia inducible factor (HIF-1), via its binding to specific response elements. The mechanism of hypoxic induction and the effect of low glucose on PDGF-B expression have not been characterised. We show that PDGF-B exhibits a novel, biphasic regulation (induction, followed by repression below basal levels) in bladder carcinoma cells cultured under chronic hypoxia. We show that the repression observed after long-term hypoxia is due to glucose-depletion and that this can also abrogate short-term hypoxic induction. This is in contrast to the previous results showing that hypoxia/hypoglycaemia elicit the same response. We also show that a putative hypoxia response element in the PDGF-B promoter is not sufficient for hypoxic induction, although it does function as a hypoxia independent enhancer element in hepatocellular carcinoma cells.
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| 27. |
- Öberg-Welsh, Charlotte, et al.
(författare)
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Mutation of C-terminal tyrosine residues Y497/Y504 of the Src-family member Bsk/Iyk decreases NIH3T3 cell proliferation
- 1998
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Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 16:2, s. 111-124
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the properties of the Src-family member Bsk/Iyk, NIH3T3 cells were transfected with wild-type Bsk/Iyk or Bsk/Iyk carrying Y497F, Y504F or Y497/504F mutations. These positions are putatively homologous to tyr-527 in Src. The Bsk/IykY497/504F cells displayed a decreased cell growth rate, parallelled by an augmentation of the fraction of cells in G1-phase. The Bsk/IykY497/504F double-mutation decreased the [3H]thymidine incorporation. No effects on NIH3T3 cell growth could be seen in cells expressing wild-type Bsk/Iyk or the other Bsk/Iyk mutants. In vitro kinase reactions performed on immunoprecipitates from NIH3T3 cells expressing wild-type or mutated Bsk/Iyk revealed increased relative [32P]-incorporation into Bsk/Iyk isoforms containing the Y504F and Y497/504F mutations compared with wild-type Bsk/Iyk. The Y497F and Y497/504F mutations elevated the proportion of [32P]-incorporation into a 57 kDa Bsk/Iyk product relative to that into the 60 kDa isoform. The Y497F Bsk/Iyk mutant not only increased the relative amount of p57 Bsk/Iyk but also transferred this isoform to the nuclear subcellular fraction. The results suggest that Bsk/Iyk has unique regulatory properties, and that this kinase might serve a role in inhibiting cell replication.
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