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31.
Identification of tyrosines 154 and 307 in the extracellular domain and 653 and 766 in the intracellular domain as phosphorylation sites in the heparin-binding fibroblast growth factor receptor tyrosine kinase (flg). 总被引:3,自引:0,他引:3 下载免费PDF全文
J. Hou K. McKeehan M. Kan S. A. Carr M. J. Huddleston J. W. Crabb W. L. McKeehan 《Protein science : a publication of the Protein Society》1993,2(1):86-92
Four tyrosine residues have been identified as phosphorylation sites in the tyrosine kinase isoform of the heparin-binding fibroblast growth factor receptor flg (FGF-R1). Baculoviral-insect cell-derived recombinant FGF-R1 was phosphorylated and fragmented with trypsin while immobilized on heparin-agarose beads. Phosphotyrosine peptides were purified by chromatography on immobilized anti-phosphotyrosine antibody and analyzed by Edman degradation and electrospray tandem mass spectrometry. Tyrosine residue 653, which is in a homologous spatial position to major autophosphorylation sites in the catalytic domain of the src and insulin receptor kinases, is the major intracellular FGF-R1 phosphorylation site. Residue 766 in the COOH-terminus outside the kinase domain is a secondary site. Tyrosine residues 154 and 307, which are in the extracellular domain of transmembrane receptor isoforms and are in an unusual sequence context for tyrosine phosphorylation, were also phosphorylated. 相似文献
32.
Koichi Matsuzaki Mikio Kan Wallace L. McKeehan 《In vitro cellular & developmental biology. Animal》1996,32(6):345-360
Summary Two transmembrane serine-threonine kinases (type I and II receptors), a membrane-anchored proteoglycan (type III), and a homodimeric
ligand participate in the transforming growth factor beta type on (TGFβ1) signal transduction complex. The expression of recombinant
receptors in insect cells co-infected with up to three recombinant baculoviruses was employed to study interactions among
the ectodomains of the three types of receptors and the TGFβ1 ligand in absence of uncontrollable extrinsic factors in mammalian
cells. Multi-subunit complexes were assembled in intact cells and purified on glutathione-conjugated beads for analysis by
tagging one of the subunits with glutathione S-transferase (GST). Intrinsic ligand-independent interactions were observed
among receptor subunits as follows: type III–III type I–I, type III-I, and type II-I. The homeotypic complex of type II–II
receptors and the heterotypic type III-II interaction was ligand dependent. The type I, but not the type III, subunit displaced
about 50% of the type II component in either ligand-dependent homomeric type II-type II complexes or heteromeric type III-type
II complexes to form type II-I or type III-II-I oligomers, respectively. The type II subunit displaced type I subunits in
oligomers of the type I subunit. Specificity of type I receptors may result from differential affinity for the type II receptor
rather than specificity for ligand. A monomeric subunit of the TGFβ1 ligand bound concurrently to type III and type II or
type III and type I receptors, but failed to concurrently bind to the type II and type I subunits. The binding of TGFβ1 to
the type I kinase subunit appears to require an intact disulfide-linked ligand dimer in the absence of a type III subunit.
The combined results suggest a pentameric TGFβ signal transduction complex in which one unit each of the type III, type II,
and type I components is assembled around the two subunits of the dimeric TGFβ1 ligand. An immobilized GST-tagged subunit
of the receptor complex was utilized to assemble multi-subunit complexesin vitro and to study the phosphorylation events among subunits in the absence of extrinsic cell-derived kinases. The results revealed
that (a) a low level of ligand-independent autophosphorylation occurs in the type I kinase; (b) a high level of autophosphorylation
occurs in the type II kinase; (c) both the type III and type I subunits aretrans-phosphorylated by the type II subunit; and (d) the presence of both type I and II kinases complexed with the type III subunit
and dimeric TGFβ1 ligand in a pentameric complex causes maximum phosphorylation of all three receptor subunits. 相似文献
33.
The degenerative changes in the spermatids as measured by changes in fine structure abnormalities increased with time following
injection of Cd2+ into rat testis. The spermatids in the twelve hours group appear as peculiarly club shaped and elongated structures with
one or two small but perceptible vacuoles. The subacrosomal area and the space between the nucleus and the middle piece are
seen abnormally dilated. In the 30 day group, the central filaments are the most susceptible unit of 9+2 axoneme complex.
The plasma membrane, the cytoplasmic matrix, the mitochondria of the middle piece and the fibrous sheath appear shrunken,
discontinuous and degenerative. 相似文献
34.
The two species of Sarcocystis--S. levinei and S. fusiformis from the water buffalo, Bubalus bubalis, show some ultrastructural similarities in their cyst wall and zoites. The zoites of both species are of about the same size, banana-shaped and have 22 subpellicular microtubules, numerous micronemes, eight rhoptries, a micropore in the region of the micronemes, an elongated mitochondrion, and a nucleus. S. levinei has 200--300 micronemes and S. fusiformis has about 400. The sarcocysts of both species are trabeculated and their cyst walls have cytophaneres containing annulated fibrils and coarse, electron dense granules. The cytophaneres of S. levinei are sloping, with irregular, wavy outlines, whereas S. fusiformis has the cauliflower-type of cytophaneres. This difference in the appearance of the cytophaneres, together with the difference in size of the sarcocysts and their definitive hosts, further confirms that S. levinei and S. fusiformis are two distinct species in the water buffalo. 相似文献
35.
黑龙江省东宁县山区蜱类的生态调查 总被引:2,自引:0,他引:2
我国东北地区有的蜱种已证实是传播森林脑炎、北亚蜱传斑疹伤寒的媒介。近年来,国内文献又报导了从东北牡丹江林区发现了莱姆病(Lyme Disease)病人,病人都有被婢咬史,并从全沟硬蜱(Ixodes persulcatus)的中 相似文献
36.
Summary A serum-free culture system supplemented with neural tissue extract for normal and tumor human esophagi was applied to the
culture of mouse esophageal epithelium. Similar to mouse mesenchyme and skin epithelium, esophageal epithelial lines (MEE)
emerged after serial culture. The cells had an apparent unlimited life span but retained morphology and other characteristics
of normal epithelial cells. The cells formed a small cyst consisting of keratined squamous epithelium in syngenic hosts. A
screen for growth factors that stimulated growth of the nonmalignant MEE cells in the absence of neural extract revealed that
epidermal growth factor (EGF) and heparin-binding (fibroblast) growth factors (HBGF) were most effective. An HBGF-like activity
was apparent in extracts of rapidly proliferating but not quiescent MEE cells at low or confluent densities. A cloned cell
line (MEE/C8) was selected from MEE cell cultures in the absence of neural extract. MEE/C8 cells proliferated independent
of either EGF or HBGF at rates equal to MEE cells, cell extracts exhibited HBGF-like activity at all stages of proliferation,
and the cells formed large invasive tumors in syngenic hosts. The HBGF-like activity present in extracts of tumorigenic MEE/C8
and proliferating nonmalignant MEE cells had properties similar to HBGF-1 (acidic fibroblast growth factor). These results
constitute a cultured mouse esophageal epithelial cell model for study of conversion of immortalized premalignant cells to
malignant cells, and suggest that conversion from a state of cell cycle-dependent autocrine expression of one or more members
of the HBGF family to a state of constitutive expression correlates with and may contribute to malignancy.
The work was supported in part by grants CA37589 and DK35310 to Dr. McKeehan, from the National Cancer Institute, Bethesda,
MD. 相似文献
37.
T Murakami T Nishiyama T Shirotani Y Shinohara M Kan K Ishii F Kanai S Nakazuru Y Ebina 《The Journal of biological chemistry》1992,267(13):9300-9306
38.
The DNA oligomer analogues 3'd(CTTTCTTT)5'-P4-5'd(TTCTTCTT)3' (IV), 5'd-(TTTCTTTC)3'-P2-3'd(CTTTCTTT)5' (V), and 5'd(TTTCTTTC)3'-P2-3'd(CTTTCTTT)5'-P4-5'd-(TTCTTCTT)3' (VI) (P2 = P*P and P4 = P*P*P*P, where P = phosphate and * = 1,3-propanediol) have been synthesized. These oligomers consist of a linker group or groups and homopyrimidine oligonucleotides which have opposite sugar-phosphate backbone polarities. These oligomer analogues are designed to form triplexes with a duplex, 5'd(AAAGAAAGCCCTTTCTTTAAGAAGAA)3'.5'd(TTCTTCTTAAA- GAAAGGGCTTTCTTT)3' (I), which contains small homopurine clusters alternately located in both strands. The length of the linker groups, P2 and P4, was based upon a computer modeling analysis. Triplex formation by the unlinked octamers 5'd(TTCTTCTT)3' (II) and 5'd(TTTCTTTC)3' (III) and the linked oligomer analogues IV-VI with the target duplex was studied by thermal denaturation at pH 5.2. The order of stabilities of triplex formation by these oligomers was I-V much much greater than I-IV greater than I-(II, III). The mixture of I and VI showed two transitions corresponding to the dissociation of the third strand. The higher transition corresponded to the dissociation of 3'-3'-linked octamer segments, and the lower one corresponded to the dissociation of 5'-5'-linked octamer segments. The Tm of the latter transition was higher than that of the I-IV triplex; thus the triplex formed by the 5'-5'-linked octamer segment was stabilized by the triplex formed by the 3'-3'-linked octamer segments in the I-VI triplex. Triplex formation of this system was also studied in the presence of ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
39.
Eldon E. Leutzinger Paul S. Miller Lou-Sing Kan 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1982,697(2):243-251
The hydrolysis of 3-methyl-2′-deoxycytidine in aqueous solution has been investigated. Varying proportions of 3-methylcytosine, 3-methyluracil and 3-methyl-2′-deoxyuridine are formed depending upon conditions of pH and temperature. All three hydrolytic products are formed at pH 6.8 and 90°C. At pH 2, depyrimidination of 3-methylcytosine occurs as the only hydrolysis product. When the pH is increased to 12, 3-methyl-2′-deoxycytidine on heating at 90°C is completely deaminated to 3-methyl-2′-deoxyuridine with few side products formed. This reaction serves as the basis for a convenient synthesis of 3-methyl-2′-deoxyuridine. The 300 MHz spectra of 3-methyl-2′-deoxycytidine and 3-methyl-2′-deoxyuridine indicate that the sugar ring in these compounds is predominantly in 2E conformation. 相似文献
40.
Decreased alpha 1-adrenoceptor responsiveness and density in liver cells of thyroidectomized rats 总被引:5,自引:0,他引:5
The effects of hypothyroidism on the hepatic alpha 1-receptor system were studied in isolated rat liver cells. Phenylephrine and vasopressin caused concentration-dependent activation of glycogen phosphorylase and release of 45Ca from 45Ca-loaded cells in either normal or thyroidectomized rats. However, the magnitude of both responses to phenylephrine was markedly suppressed after thyroidectomy and could be restored to near normal levels by in vivo treatment with 1-triiodothyronine (0.25 mg/kg/day) for 4 days. The potency of vasopressin to induce phosphorylase activation and 45Ca release was only slightly reduced by thyroidectomy. Binding of [3H]prazosin to putative alpha 1-receptors in purified liver plasma membranes revealed that the above changes were accompanied by a decrease in the density of binding sites from 567 +/- 51 fmol/mg of protein in controls to 326 +/- 51 fmol/mg in thyroidectomized rats and a return to 498 +/- 23 fmol/mg in thyroidectomized rats treated with 1-triiodothyronine. The affinity of binding sites for [3H]prazosin or for alpha-receptor agonists was the same in the three groups of rats and affinity for epinephrine was unaffected by the presence of guanyl-5'-yl imidodiphosphate (30-100 microM). From these findings, it appears that a reduction in the number of hepatic alpha 1-receptors is responsible for the selective decrease in alpha-adrenergic responses in the hypothyroid rat liver. These changes are opposite to those previously reported for hepatic beta-receptors. 相似文献