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991.
Molecular cloning of mammalian Spred-3 which suppresses tyrosine kinase-mediated Erk activation 总被引:8,自引:0,他引:8
Kato R Nonami A Taketomi T Wakioka T Kuroiwa A Matsuda Y Yoshimura A 《Biochemical and biophysical research communications》2003,302(4):767-772
We have reported on Spred-1 and Spred-2, which inhibit MAP kinase activation by interacting with c-kit and ras/raf. Here, we report the cloning of a third member in this family, Spred-3. Spred-3 is expressed exclusively in the brain and its gene locates in chromosome 19q13.13 in human. Like Spred-1 and -2, Spred-3 contains an EVH1 domain in the N-terminus and a Sprouty-related cysteine-rich region (SPR domain) in the C-terminus that is necessary for membrane localization. However, Spred-3 does not possess a functional c-kit binding domain (KBD), since the critical amino acid Arg residue in this region was replaced with Gly in Spred-3. Although Spred-3 suppressed growth factor-induced MAP kinase (Erk) activation, inhibitory activity of Spred-3 was lower than that of Spred-1 or Spred-2. By the analysis of chimeric molecules between Spred-3 and Spred-1, we found that the SPR domain, rather than KBD, is responsible for efficient Erk suppression. The finding of Spred-3 revealed the presence of a novel family of regulators for the Ras/MAP kinase pathway, each member of which may have different specificities for extracellular signals. 相似文献
992.
Ogawa T Shiga K Hashimoto S Kobayashi T Horii A Furukawa T 《Biochemical and biophysical research communications》2003,306(2):537-543
We have found a novel alternative splicing product of the apoptotic protease activating factor 1 (APAF-1), termed APAF-1-ALT, in the LNCaP human prostate cancer cell line. APAF-1-ALT harbors the caspase recruitment domain and an incomplete CED-4 like/ATPase domain, but lacks the WD-40 repeat units. The LNCaP cell expressed the full-length APAF-1 weakly and APAF-1-ALT rather abundantly, especially after mycoplasma infection. LNCaP underwent a retarded DNA damage-induced apoptosis, which was independent of caspase 9 activity. APAF-1-ALT functioned less effectively in inducing apoptosis than did APAF-1-XL, the full-length APAF-1, in transient transfection. Moreover, APAF-1-ALT interfered with APAF-1-XL's ability to induce apoptosis in transient double transfection experiment. These results indicate that APAF-1-ALT is a molecule that is deficient and impeded for mediating apoptosis and that it may contribute to the resistance to DNA damage-induced treatment observed in LNCaP. 相似文献
993.
The transport of dipeptides and beta-lactam antibiotics across the rat renal basolateral membrane was examined. The initial uptake of glycylsarcosine and cefadroxil by rat renal basolateral membrane vesicles was inhibited by the presence of all the di- and tripeptides and beta-lactam antibiotics that were tested in this study. However, the uptake of both substrates was not inhibited by glycine, an amino acid. The initial uptake of zwitterionic beta-lactam antibiotics, cefadroxil, cephradine, and cephalexin, was stimulated by preloaded glycylsarcosine (countertransport effect). On the other hand, the uptake of dianionic beta-lactam antibiotics, ceftibuten and cefixime, was not affected. A concentration-dependent initial uptake of glycylsarcosine and cefadroxil suggested the existence of a carrier-mediated mechanism, whereas the transport of ceftibuten did not show any saturated uptake. The transporter that participates in the permeation of dipeptides and beta-lactam antibiotics across basolateral membranes showed lower affinity than did PEPT1 and PEPT2. This is the first study that showed an evidence for a peptide transporter, expressed in the rat renal basolateral membrane, that recognizes zwitterionic beta-lactam antibiotics using basolateral membrane vesicles isolated from normal rat kidney. 相似文献
994.
995.
996.
Genetic complementation in female (BXSB x NZW)F2 mice 总被引:1,自引:0,他引:1
Kono DH Park MS Theofilopoulos AN 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(12):6442-6447
F(1) hybrids among New Zealand Black (NZB), New Zealand White (NZW), and BXSB lupus-prone strains develop accelerated autoimmunity in both sexes regardless of the specific combination. To identify BXSB susceptibility loci in the absence of the Y chromosome accelerator of autoimmunity (Yaa) and to study the genetics of this complementation, genome-wide quantitative trait locus (QTL) mapping was performed on female (BXSB x NZW)F(2) mice. Six QTL were identified on chromosomes 1, 4, 5, 6, 7, and 17. Survival mapped to chromosomes 5 and 17, anti-chromatin Ab to chromosomes 4 and 17, glomerulonephritis to chromosomes 6 and 17, and splenomegaly to chromosomes 1, 7, and 17. QTL on chromosomes 4 and 6 were new and designated as Lxw1 and -2, respectively. Two non-MHC QTL (chromosomes 1 and 4) were inherited from the BXSB and the rest were NZW-derived, including two similar to previously defined loci. Only two of 11 previously defined non-MHC BXSB QTL using male (Yaa(+)) crosses were implicated, suggesting that some male-defined BXSB QTL may require coexpression of the Yaa. Findings from this and other studies indicate that BXSB and NZB backgrounds contribute completely different sets of genes to complement NZW mice. Identification of susceptibility genes and complementing genes in several lupus-prone strain combinations will be important for defining the epistatic effects and background influences on the heterogeneous genetic factors responsible for lupus induction. 相似文献
997.
The calmodulin-binding domain of myristoylated alanine-rich C kinase substrate (MARCKS), which interacts with various targets including calmodulin, actin and membrane lipids, has been suggested to function as a crosstalk point among several signal transduction pathways. We present here the crystal structure at 2 A resolution of a peptide consisting of the MARCKS calmodulin (CaM)-binding domain in complex with Ca2+-CaM. The domain assumes a flexible conformation, and the hydrophobic pocket of the calmodulin N-lobe, which is a common CaM-binding site observed in previously resolved Ca2+-CaM-target peptide complexes, is not involved in the interaction. The present structure presents a novel target-recognition mode of calmodulin and provides insight into the structural basis of the flexible interaction module of MARCKS. 相似文献
998.
Jie?Zhang Taichi?Taniguchi Toru?TakitaEmail author Ahyaudin B.?Ali 《Ichthyological Research》2003,50(4):310-317
Epidermal structures of three species of Periophthalmus (Ps.) and two species of Periophthalmodon (Pn.) were investigated in relation to their lifestyle. All species of both genera lack a dermal bulge, which species of other two oxudercine genera, Boleophthalmus and Scartelaos, have in their epidermis. In Periophthalmus and Periophthalmodon species, which are highly terrestrial, the middle cells are well developed in the epidermis and the capillaries are distributed in the surface of the epidermis on the head and dorsal body. In Periophthalmus species and Pn. septemradiatus, the capillaries and blood vessels are also distributed in the epidermis of the abdomen, superficially in Ps. modestus and deeply in other species. In Ps. modestus, the capillaries are also densely distributed on the surface of the epidermis in the caudal area, whereas in other species, the epidermal capillaries and blood vessels of this area are located deep with a very low density. In Pn. schlosseri, the epidermal capillaries are not found in either the abdominal area or caudal area. A comparison of the distribution of epidermal capillaries among Boleophthalmus, Periophthalmodon, Periophthalmus, and Scartelaos species revealed that the skin makes a larger contribution to respiration in the species having a more terrestrial lifestyle. Goblet mucous cells are completely lacking in Periophthalmus species, whereas slimelike materials were often found on the skin surface of Periophthalmus species. This finding suggests that Periophthalmus species have some unknown mechanism for producing mucus. In Pn. schlosseri, exposure of the dense capillary net on the surface of the head is likely to increase cutaneous respiration, but it also makes the fish an attractive target of bloodsucking insects.Supplementary material to this paper is available in electronic format at http://dx.doi.org/10.1007/s10228-003-00173-7 相似文献
999.
1000.
Kohno T Sasaki T Kobayashi K Fainzilber M Sato K 《The Journal of biological chemistry》2002,277(39):36387-36391
The three-dimensional solution structure of delta-conotoxin TxVIA, a 27-mer peptide agonist/antagonist of sodium channels, was determined by two-dimensional (1)H NMR spectroscopy with simulated annealing calculations. A total of 20 converged structures of delta-conotoxin TxVIA were obtained on the basis of 360 distance constraints obtained from nuclear Overhauser effect connectivities, 28 torsion angle constraints, and 27 constraints associated with hydrogen bonds and disulfide bonds. The atomic root mean square difference about the averaged coordinate positions is 0.35 +/- 0.07 A for the backbone atoms (N, C(alpha), C) and 0.98 +/- 0.14 A for all heavy atoms of the entire peptide. The molecular structure of delta-conotoxin TxVIA is composed of a short triple-stranded antiparallel beta-sheet. The overall beta-sheet topology is +2x, -1, which is the same as those for other conotoxins. However, the three-dimensional structure of delta-conotoxin TxVIA has an unusual hydrophobic patch on one side of the molecule, which may play an important role in the sodium channel binding. These results provide a molecular basis for understanding the mechanism of sodium channel modulation through the toxin-channel interaction and insight into the discrimination of different ion channels. 相似文献