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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.
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PMID:Role of non-TSH factors in thyroid cell growth. 347 6

In the human neuroblastoma cell line SH-SY5Y, insulin-like growth factors I (IGF-I) and II (IGF-II) are established mitogens, and IGF-I appears to promote SH-SY5Y neuronal differentiation. Studies show that c-myc gene product is a transcription factor associated with cell proliferation, and that c-myc messenger RNA levels decrease in differentiating SH-SY5Y neurons. Using Northern analysis we show that 24 h exposure of SH-SY5Y cells to IGF-I (3-10 nM) causes a 3- to 5-fold decrease in c-myc expression. The decrease in c-myc expression due to IGF-I is mediated via the type I IGF receptor and coincides with an IGF-I-mediated induction of the neuronal differentiation markers growth cone associated protein 43 and tissue type plasminogen activator. Under these conditions, IGF-I (10 nM) did not markedly affect the levels of Max messenger RNA expression. Thus, the differentiation promoting activity of IGF-I in SH-SY5Y cells in part due to IGF-I-dependent regulation of the expression of genes involved in neuronal differentiation.
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PMID:Insulin-like growth factor I regulates c-myc and GAP-43 messenger ribonucleic acid expression in SH-SY5Y human neuroblastoma cells. 847 53

We examined the effects of insulin-like growth factor (IGF)-I on follicular growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator (PA) activity in vitro, using a perfused rabbit ovary preparation in order to determine whether the follicle-stimulating effects of growth hormone (GH) are mediated by IGF-I. The addition of IGF-I to the perfusate stimulated follicular growth and the resumption of meiosis in follicular oocytes in a dose-dependent manner. There was no significant difference in the production of progesterone by perfused rabbit ovaries between IGF-I-treated and control ovaries, whereas IGF-I increased the production of estradiol (E2) by perfused rabbit ovaries in a dose-dependent manner. The concomitant addition of a monoclonal antibody recognizing the type I IGF receptor, alpha IR-3, to the perfusate significantly blocked IGF-I-stimulated follicular growth, oocyte maturation, and E2 production. Intrafollicular PA activity increased significantly 4 h after exposure to 10 or 100 ng/ml of IGF-I and reached maximal levels at 6 h. The percentage increase in follicle diameter at 6 h after exposure to IGF-I was significantly correlated with the intrafollicular PA activity. Treatment with GH resulted in a 2.7-fold increase in intrafollicular levels of IGF-I mRNA. The binding of [125I]-IGF-I to rabbit ovarian membrane preparations was inhibited by unlabeled IGF-I and IGF-II in a concentration-dependent manner. The relative affinity of the IGF-I receptor for IGF-I, IGF-II, and insulin was typical of type I binding (IGF-I > IGF-II > insulin). Affinity cross-linking of ovarian membranes with [125I]-IGF-I revealed a radiolabeled band corresponding to a molecular weight of 135,000, the alpha subunit of the type I IGF receptor. This band was totally displaced by IGF-I and alpha IR-3. It was concluded that IGF-I stimulated follicular development, E2 production, and oocyte maturation by interacting with its specific receptor located in rabbit ovarian membranes.
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PMID:Effects of insulin-like growth factor-I on follicle growth, oocyte maturation, and ovarian steroidogenesis and plasminogen activator activity in the rabbit. 879 70

Insulin-like growth factors (IGF-I and -II) play an active role in cell proliferation. In biological fluids, they are non-covalently bound to high-affinity binding proteins (IGFBPs), at least 6 species of which have been identified to date, but with poorly defined functions. One of these IGFBPs, IGFBP-2, is secreted by most cell lines and appears to be involved in cell proliferation. A human epidermoid carcinoma cell line, KB 3.1, which produces IGFBP-1 and -3 and small amounts of IGFBP-4, but no IGFBP-2, was stably transfected with an expression vector comprising IGFBP-2 complementary DNA (cDNA), whose expression was placed under the control of the constitutive and ubiquitous cytomegalovirus promoter. After an s.c. injection of these IGFBP-2-expressing KB 3.1 cells into nude mice, tumours developed more quickly than in controls, they were 3 to 4 times larger and grew about 3 times as fast. Concomitant with IGFBP-2 expression in these tumours, were a decrease in IGFBP-1 expression and an increase in IGFBP-3 proteolysis, both of which increase the bioavailability of the IGF-II produced by the cells. The increased IGFBP-3 proteolysis most probably resulted from amplified expression of tissue-type plasminogen activator (t-PA) and depression of its inhibitor (PAI-I) observed in IGFBP-2-expressing xenografts. Our findings suggest that IGFBP-2 plays a role in this model of experimental tumorigenesis via a mechanism that remains unclear, but appears to involve increased protease activity and IGF-II bioavailability.
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PMID:IGFBP-2 expression in a human cell line is associated with increased IGFBP-3 proteolysis, decreased IGFBP-1 expression and increased tumorigenicity. 971 57

The IGF-II/mannose 6-phosphate receptor (IGF2R) function in extracellular matrix (ECM) remodeling is known to occur as a result of transforming growth factor-beta (TGF-beta) activation and plasmin in the proteolytic cleavage level caused by the interaction between latent TGF-beta and urokinase plasminogen activator receptor (uPAR) respectively. In one of our previous studies, we found IGF-II and IGF2R dose-dependently correlated with the progression of pathological hypertrophy remodeling following complete abdominal aorta ligation. However, how this IGF2R signaling pathway responds specifically to IGF-II and regulates the myocardial ECM remodeling process is unclear. We found that IGF2R was aberrantly expressed in myocardial infarction scars. The matrix metalloproteinase-9 (MMP-9) zymographic activity was elevated in H9c2 cardiomyoblast cells treated with IGF-II, but not IGF-I. Treatment with Leu27IGF-II, an IGF2R specifically binding IGF-II analog, resulted in significant time-dependent increases in the MMP-9, tissue-type plasminogen activator (tPA), and urokinase plasminogen activator (uPA); and a reduction in the tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) protein expression. Furthermore, IGF2R expression inhibition by siRNA blocked the IGF-II-induced MMP-9 activity. We hypothesize that after IGF-II is bound with IGF2R, the resulting signal disrupts the balance in the MMP-9/TIMP-2 expression level and increases plasminogen activator (PAs) expression involved in the development of myocardial remodeling. If so, IGF2R signaling inhibition may have potential use in the development of therapies preventing heart fibrosis progression.
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PMID:IGF-II/mannose 6-phosphate receptor activation induces metalloproteinase-9 matrix activity and increases plasminogen activator expression in H9c2 cardiomyoblast cells. 1849 91