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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step in the action of many growth factors is to bind to the receptors and to stimulate autophosphorylation of the receptors on tyrosine residues. The receptors then form high-affinity physical complexes with cytoplasmic signaling molecules (Fig. 8). It is not clear whether the function of the complexes is to localize signaling molecules at the plasma membrane or to position the molecules to be favored substrates of the receptor. It is also not necessarily true that each receptor molecule binds more than one signaling molecule at a time. We have shown that each of the signaling molecules that binds to the PDGF receptor recognizes a specific site in the receptor cytoplasmic domain. A phosphotyrosine on the receptor is an important determinant of the interaction with the signaling molecule. However, the specificity of the interaction is determined by the receptor sequence surrounding each phosphotyrosine, especially the sequences on the carboxy-terminal side of the tyrosine. SH2 regions of the signaling molecules appear to bind directly to the specific recognition sequences on the receptor. Thus, the intracellular protein-protein interactions that depend on SH2 domains binding to phosphotyrosine are not as random as we once believed but are part of a highly specific system of interactions between tyrosine-phosphorylated proteins and SH2-containing signaling proteins. A major role of tyrosine kinase appears to be in creating specific recognition sites that bind SH2 domains. By elucidating the specificity of these interactions, we have been able to selectively block some interactions while allowing others to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
Cold Spring Harb Symp Quant Biol 1991
PMID:Interactions of growth factor receptors with cytoplasmic signaling molecules. 166 83

Incubation of Swiss 3T3 murine fibroblasts at low temperatures induces phosphorylation on tyrosine of a transmembrane protein of 175 kDa. This phenomenon is time and temperature dependent and reaches a maximum after 2 hr at 4 degrees C. The 175 kDa protein phosphorylated in vivo at low temperatures can be immunoprecipitated by phosphotyrosine antibodies and displays auto-kinase activity in vitro in the presence of radiolabelled ATP. This molecule was found to react with anti-peptide antibodies directed against the product of the HER2/neu proto-oncogene only when immunoprecipitated with phosphotyrosine antibodies from cold-stimulated cells. Activation of protein kinase-C by treatment of the cells with phorbol esters, bombesin or PDGF inhibits the effect of the exposure to low temperatures. Phosphorylation of p175 is not induced by treatment of the cells with the phosphatases inhibitor sodium orthovanadate. These results suggest that, at low temperatures, the tyrosine kinase associated with the putative receptor encoded by c-neu is activated by physico-chemical modifications of the plasma membrane.
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PMID:Ligand-independent tyrosine phosphorylation of the receptor encoded by the c-neu oncogene. 168 56

To explain the insulin resistance induced by catecholamines, we studied the tyrosine kinase activity of insulin receptors in a state characterized by elevated noradrenaline concentrations in vivo, i.e. cold-acclimation. Insulin receptors were partially purified from brown adipose tissue of 3-week- or 48 h-cold-acclimated mice. Insulin-stimulated receptor autophosphorylation and tyrosine kinase activity of insulin receptors prepared from cold-acclimated mice were decreased. Since the effect of noradrenaline is mediated by cyclic AMP and cyclic AMP-dependent protein kinase, we tested the effect of the purified catalytic subunit of this enzyme on insulin receptors purified by wheat-germ agglutinin chromatography. The catalytic subunit had no effect on basal phosphorylation, but completely inhibited the insulin-stimulated receptor phosphorylation. Similarly, receptor kinase activity towards exogenous substrates such as histone or a tyrosine-containing copolymer was abolished. This inhibitory effect was observed with receptors prepared from brown adipose tissue, isolated hepatocytes and skeletal muscle. The same results were obtained on epidermal-growth-factor receptors. Further, the catalytic subunit exerted a comparable effect on the phosphorylation of highly purified insulin receptors. To explain this inhibition, we were able to rule out the following phenomena: a change in insulin binding, a change in the Km of the enzyme for ATP, activation of a phosphatase activity present in the insulin-receptor preparation, depletion of ATP, and phosphorylation of a serine residue of the receptor. These results suggest that the alteration in the insulin-receptor tyrosine kinase activity induced by cyclic AMP-dependent protein kinase could contribute to the insulin resistance produced by catecholamines.
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PMID:Effect of cyclic AMP-dependent protein kinase on insulin receptor tyrosine kinase activity. 282 14

In the experiments described above, a neutralizing anti-ras antibody was utilized to study the role of ras protein in normal cell proliferation. Initially, it was demonstrated that the antibody was specific for ras protein, and that ras activity was efficiently inhibited. With the neutralizing antibody, it was first shown that ras activity is required for the proliferation of all normal cell types tested. ras activity was required just prior to initiation of S phase. The transforming activity of several retroviral oncogenes was also blocked following anti-ras injection. This included the tyrosine kinase, plasma-membrane-associated proteins, and an oncogene derived from a growth factor. On the other hand, cytoplasmic oncogenes with serine kinase activity were not dependent on ras activity for expression of the transformed phenotype. These observations form the basis of our model for proliferative signal transduction. We propose that the action of either growth factors, their receptor molecules, or related oncogenes initiate an intracellular signal received by ras proteins and then transferred by ras to cytoplasmic serine kinase oncogenes. This signal transduction system directly regulates cellular proliferation. Although further evidence in support of this model is needed, it appears from our studies that the mechanism of signaling between tyrosine kinases and ras proteins might be at the level of phospholipid metabolism. This observation is based on the fact that the mitogenic lipid molecules tested were remarkably dependent on ras activity, even more so than the growth factors or related oncogenes tested. Finally, our work suggests a fundamental distinction between normal and tumor cells. All the normal cell types tested were efficiently inhibited in proliferation by the injected antibody. Tumor cells, on the other hand, were never completely inhibited by the antibody and often were not inhibited at all. The presence of an activated ras oncogene within the tumor assured at least a partial role for ras activity in the proliferation of the mature tumor line. The significance of the observed distinction between normal and tumor cells is not known. The fact that this distinction involves a protein with an apparently critical role in normal proliferation suggests that the observation might be important.
Cold Spring Harb Symp Quant Biol 1988
PMID:Critical role of cellular ras proteins in proliferative signal transduction. 307 1

Protein phosphorylation at tyrosine residues is believed to be involved in several important cellular processes because tyrosine-specific protein kinase activation is associated with stimulation of cellular proliferation by hormones and growth factors, embryogenesis, and retroviral cell transformation. Because cell proliferation is thought to be an essential component of chemical carcinogenesis, liver tyrosine-specific protein kinase activity was examined during the early stages of the Solt and Farber chemical hepatocarcinogenesis model. Rats were given diethylnitrosamine in one dose (200 mg/kg, IP) followed by 2 weeks of dietary 0.02% 2-acetylamino-fluorene starting at day 14 after diethylnitrosamine, followed by partial hepatectomy on day 21. By day 32 this regimen produces a relatively synchronized population of hyperplastic liver nodules up to 1.5 mm in diameter. Rats were sacrificed on day 32, their livers were perfused with cold normal saline, homogenized, and centrifuged at 1,000g for 10 min. The resulting supernatant was centrifuged at 30,000g for 30 min and the pellet was assayed for tyrosine kinase activity using the synthetic peptide [Val5]angiotensin II as substrate. Rats that received the complete regimen had a 2.6-fold increase in their liver tyrosine kinase activity as compared to sham controls (2.4 pmoles/min/mg protein vs 6.4 pmoles/min/mg protein, P less than .05). In contrast, rats that received a partial regimen (ie, partial hepatectomy, or 2-acetylaminofluorene + partial hepatectomy, or diethylnitrosamine + 2-acetylaminofluorene) did not have elevated tyrosine kinase activity nor did they have hyperplastic nodules. These preliminary data suggest that activation of liver tyrosine kinase is associated with the very early stages of chemical hepatocarcinogenesis.
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PMID:Liver tyrosine kinase activation during early stages of chemical hepatocarcinogenesis. 403 31

Insulin and insulin-like growth factor-1 (IGF-1) receptors were quantified in glycoprotein fractions prepared by wheat germ agglutinin-agarose affinity chromatography from skeletal muscle of several species of salmonid fish and carp. Insulin binding in fish skeletal muscle was lower than insulin binding found in rat. IGF-1-specific binding was two- to sixfold higher than insulin binding (16.0 +/- 3.0 versus 5.8 +/- 0.75%/50 micrograms glycoprotein in brown trout, 15.5 +/- 0.9 versus 2.2 +/- 0.5%/50 micrograms in coho salmon, and 39.7 +/- 7.6 versus 16.0 +/- 3.0%/50 micrograms in carp muscle). Specific IGF-1 binding in fish skeletal muscle presented values similar to those in rat muscle. IGF-1 receptor binding was, in addition, highly specific. Cold IGF-1 displaced radiolabeled IGF-1 binding in doses 100- to 1000-fold lower than cold insulin (ED50 of IGF-1 binding to carp receptor preparations was 0.24 +/- 0.04 nM when displaced with cold IGF-1 and 368 +/- 83 nM when displaced with insulin). On the other hand, cold insulin displaced radiolabeled insulin binding at concentrations 10- to 100-fold lower than cold IGF-1. Receptor tyrosine kinase activity was stimulated over basal values in a dose-dependent manner by both insulin and IGF-1, although IGF-1 was more potent than insulin. Basal rates of phosphorus transferred to the artificial exogenous substrate poly(Glu4:Tyr1) were similar in all salmonid species (200-320 fmol P/micrograms protein) and higher in carp (1840 +/- 300 fmol P/micrograms protein). Maximum percentage of stimulation of tyrosine kinase activity by insulin and IGF-1 was in the same range in all salmonid species and carp (130-200% for insulin, 160-232% for IGF-1). Abundance of IGF-1 receptors in fish skeletal muscle contrasts with the pattern observed in higher vertebrates, in which insulin receptors prevail over IGF-1 receptors.
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PMID:Abundant insulin-like growth factor-1 (IGF-1) receptor binding in fish skeletal muscle. 778 61

We have isolated a cDNA that encodes a novel member of the Y-box binding protein family, termed as RYB-a (Rat Y-box Binding protein-a). RYB-a is a 31 kDa protein that contains a conserved cold-shock domain and an amino acid alignment similar to those of charge zipper proteins. Expression of RYB-a mRNA was highly abundant in the skeletal muscle, spleen, and fetal liver. The expression is very low in new-born and adult livers, suggesting its expression is under developmental regulation. In addition, the expression of RYB-a mRNA was induced in the liver during regeneration and by stimulation of quiescent fibroblast cells with serum. Induction in the fibroblasts was inhibited by treating the cell with a specific tyrosine kinase inhibitor, genistein or by detachment of cell-adhesion. Since both treatments are known to inhibit G1 cells to enter S phase, RYB-a gene is thought to be a member of growth-inducible genes.
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PMID:A novel growth-inducible gene that encodes a protein with a conserved cold-shock domain. 802 9

To determine if aberrant expression of tyrosine kinase growth factor receptors may be related to the cell transformation capabilities of human T-lymphotropic viruses (HTLVs), we examined the expression of the epidermal growth factor receptor (EGF-R), insulin receptor (INS-R), and insulin-like growth factor receptor type-I (IGFR-I) in cell lines infected with HTLV type I (MT-2, HuT-102) and HTLV type II (Mo-T). Levels of mRNA transcripts for IGFR-I were significantly higher in both MT-2, HuT-102 (HTLV-I) and Mo-T (HTLV-II) cell lines than in uninfected cell lines (HuT-78, Jurkat); no detectable levels of EGF-R or INS-R mRNA transcript were observed in HTLV-infected or uninfected cell lines. Southern blot analysis demonstrated that no amplification or rearrangement of the IGFR-I gene occurred in either the MT-2 or Mo-T cell line. Flow cytometry analysis demonstrated that while IGFR-I protein was constitutively expressed on the cell surface in both MT-2 and Mo-T cell lines, neither EGF-R nor INS-R proteins could be detected. Ligand binding studies with MT-2 and Mo-T cell lines demonstrating binding of 125I insulin-like growth factor type-1 (IGF-I) in a dose-dependent manner and this response could be inhibited by increasing concentrations of cold IGF-I. These data demonstrate that deregulated expression of functional IGFR-I, the regular component of the growth control machinery of normal cells, may contribute to cellular proliferation and eventual transformation in HTLV-I- and HTLV-II-infected cell lines.
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PMID:Over expression of insulin-like growth factor receptor type-I in T-cell lines infected with human T-lymphotropic virus types-I and -II. 842 77

Insulin and insulin-like growth factor-I (IGF-I) receptors were characterized in glycoprotein fractions prepared by wheat germ agglutinin-agarose affinity chromatography from the ovaries of carp. Insulin-specific overall binding in carp ovaries was 6- to 11-fold lower than IGF-I binding (2.7 +/- 0.48% vs. 22.8 +/- 3.6% per 20 microg glycoprotein). Cold IGF-I displaced radiolabeled IGF-I binding in doses 1000- to 3000-fold lower than cold insulin. On the other hand, cold insulin displaced radiolabeled insulin binding at concentrations 5- to 30-fold lower than cold IGF-I. The alpha-subunit molecular masses of carp insulin and IGF-I receptors were smaller than the alpha-subunit molecular mass of rat insulin receptor (125 and 120 vs. 135 kDa, respectively). Autophosphorylation of carp beta-subunit insulin and IGF-I receptors showed similar molecular masses that did not differ from the molecular mass of rat insulin beta subunit. Receptor tyrosine kinase activity was stimulated in a dose-dependent manner by insulin and IGF-I. Insulin and IGF-I stimulated tyrosine kinase activity and reached a maximum, respectively, of 224 +/- 14% and 279 +/- 7% of basal phosphorylation. Insulin and IGF-I binding characteristics were measured through different stages of follicular development. High specific binding of both peptides in primary oocyte growth (5.6 +/- 0.8% and 50 +/- 10% per 20 microg glycoprotein for insulin and IGF-I, respectively) decreased to a minimum at the end of vitellogenesis, followed by a slight increase later, in the preovulatory stage. The presence of insulin and IGF-I receptors in carp ovaries and the changes in percentage of binding throughout the reproductive cycle suggest that, in carp, the roles of insulin and IGF-I depend on the ovarian maturation stage.
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PMID:Characterization of insulin and insulin-like growth factor-I ovarian receptors during the reproductive cycle of carp (Cyprinus carpio). 916 Jul 10

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti-VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody anti-phosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.
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PMID:Tat-human immunodeficiency virus-1 induces human monocyte chemotaxis by activation of vascular endothelial growth factor receptor-1. 926 52


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