Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence linking bacterial vaginosis (BV) to chorioamnionitis and spontaneous preterm birth is mounting. Successful treatment of BV could reduce the rate of late miscarriage and preterm birth. Mucinase and sialidase activity have been implicated in the pathogenesis of BV. This study extends the work of previous studies to investigate sialidase, other known mucin degrading enzymes and overall mucin degrading activity in samples of vaginal fluid from women with and without BV. Samples from 31 women were diagnosed for BV, and tested for enzyme activity using established assays. Activity was recorded in all samples. Significant increases in activity were detected in BV samples for sialidase using a mucin (BSM P<0.005) and serum type glycoprotein (AGP P<0.005) substrates, beta-galactosidase (P<0.001), and beta-N-acetylhexosaminidase (P<0.01). No significant increases in BV patients were detected in O-glycanase, proteinase, arylesterase, sulphatase or whole mucinase activities. These results support the hypothesis that certain BV-associated enzymes may detrimentally affect the mucosal barrier, permitting bacteria access to the uterus.
Int J STD AIDS 1999 Jul
PMID:Mucinase and sialidase activity of the vaginal microflora: implications for the pathogenesis of preterm labour. 1045 78

The TEC-2 antigenic determinant is a carbohydrate epitope located on a glycoprotein carrier molecule. In the mouse, this epitope is expressed on the zona pellucida and plasma membrane of the oocyte and is associated with the ZP2 glycoprotein and involved in the secondary sperm receptor mechanism. On the bovine oocyte expression is confined to the plasma membrane. The aim of this study was to determine the role the TEC-2 epitope plays during fertilization in the bovine species using the monoclonal antibody TEC-02. Incubating oocytes with the TEC-02 antibody prior to fertilization inhibited cleavage in a dose-dependent manner-the cleavage rate decreased as the concentration of the antibody increased. Significantly more sperm were bound to oocytes exposed to TEC-02 (12 sperm/oocyte) compared to oocytes that were not incubated with the antibody (4 sperm/oocyte). Oocytes treated with the TEC-02 antibody had a 7.5 +/- 3.2% fusion rate and no cortical granule exocytosis compared with oocytes not exposed to the antibody, with 86.5 +/- 5.8% of sperm-oocyte fusions and release of cortical granules. The block to sperm-oocyte fertilization observed in the pretreated group was overcome using intracytoplasmic sperm injection as the method of fertilization that bypassed the fusion process. Although sperm were binding to the oolemma these results suggest that fusion was not occurring and this may be due to the antibody occupying TEC-2 epitope sites involved in the fusion process. In conclusion, the TEC-2 epitope seems to be involved in sperm-oocyte interaction in the bovine species and appears to be involved specifically during the fusion events of fertilization.
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PMID:Inhibition of bovine sperm-oocyte fusion by a monoclonal antibody recognising the TEC-2 epitope on bovine oocytes. 1047 77

In Brassica, two self-incompatibility genes, encoding SLG (S locus glycoprotein) and SRK (S-receptor kinase), are located at the S locus and expressed in the stigma. Recent molecular analysis has revealed that the S locus is highly polymorphic and contains several genes, i.e., SLG, SRK, the as-yet-unidentified pollen S gene(s), and other linked genes. In the present study, we searched for expressed sequences in a 76-kb SLG/SRK region of the S(9) haplotype of Brassica campestris (syn. rapa) and identified 10 genes in addition to the four previously identified (SLG(9), SRK(9), SAE1, and SLL2) in this haplotype. This gene density (1 gene/5.4 kb) suggests that the S locus is embedded in a gene-rich region of the genome. The average G + C content in this region is 32.6%. An En/Spm-type transposon-like element was found downstream of SLG(9). Among the genes we identified that had not previously been found to be linked to the S locus were genes encoding a small cysteine-rich protein, a J-domain protein, and an antisilencing protein (ASF1) homologue. The small cysteine-rich protein was similar to a pollen coat protein, named PCP-A1, which had previously been shown to bind SLG.
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PMID:Genomic organization of the S locus: Identification and characterization of genes in SLG/SRK region of S(9) haplotype of Brassica campestris (syn. rapa). 1047 21

The cytokine interleukin 6 (IL-6), a major mediator of immune and acute phase responses of the liver, has been implicated in the termination of pregnancy once expressed in the uterus. This study was undertaken to investigate the expression and regulation of genes encoding IL-6 and IL-6 receptor (IL-6R) in rat decidual tissue. Total RNA obtained from rat decidual tissue on different days of pseudopregnancy was analyzed by RT-PCR using specific primers for IL-6, IL-6R, and 130-kDa glycoprotein (gp130). Ribosomal L19 primers served as an internal control. IL-6R and gp130 were found to be expressed in the decidua throughout development, while no messenger RNA (mRNA) for IL-6 was detected. Interestingly, within several hours of culture, decidual explants acquired the ability to express IL-6. The apparent ability of decidual cells to express IL-6 and its lack of expression in vivo led us to examine whether the IL-6 gene is actively inhibited. Primary decidual cells were cultured in the presence of estradiol, progesterone, or PRL. Progesterone showed no effect, whereas estradiol and PRL reduced the level of IL-6 mRNA expression. To examine the mechanism by which these hormones inhibit IL-6 expression, we used a simian virus 40-transformed decidual cell line (GG-AD), which expresses only estrogen receptor-beta (ERbeta). Like primary decidual cells in culture, GG-AD cells express IL-6, IL-6R, and gp130 mRNA. When cultured in the presence of estradiol (0-100 ng/ml), mRNA for IL-6 and its receptor components were down-regulated in a dose-dependent manner. Estradiol also caused a dose-dependent decrease in IL-6 protein secretion into the culture medium. The inhibitory effect of estradiol on IL-6 mRNA expression was reversed by the antiestrogen ICI-164,384. Similar inhibition of IL-6 and gp130 mRNA expression was observed with PRL treatment. However, PRL had no effect on IL-6R mRNA levels. PRL inhibition of IL-6 expression was totally reversed by tyrphostin AG490, a JAK2 inhibitor. In summary, the results of this investigation indicate that IL-6 expression, which is detrimental to the maintenance of pregnancy, is inhibited in the rat decidual tissue. This inhibition is induced by PRL and estradiol, which down-regulate not only IL-6 expression, but also the expression of IL-6 receptor and signaling proteins. The results also suggest that PRL signaling to the IL-6 gene is mediated through the long form of PRL receptor and involves JAK2 activation, whereas that of estradiol can be transduced by estrogen receptor-beta.
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PMID:The expression of interleukin-6 (IL-6), IL-6 receptor, and gp130-kilodalton glycoprotein in the rat decidua and a decidual cell line: regulation by 17beta-estradiol and prolactin. 1049 97

Many flowering plants possess self-incompatibility (SI) systems that prevent inbreeding. In Brassica, SI is controlled by a single polymorphic locus, the S locus. Two highly polymorphic S locus genes, SLG (S locus glycoprotein) and SRK (S receptor kinase), have been identified, both of which are expressed predominantly in the stigmatic papillar cell. We have shown recently that SRK is the determinant of the S haplotype specificity of the stigma. SRK is thought to serve as a receptor for a pollen ligand, which presumably is encoded by another polymorphic gene at the S locus. We previously have identified an S locus gene, SP11 (S locus protein 11), of the S(9) haplotype of Brassica campestris and proposed that it potentially encodes the pollen ligand. SP11 is a novel member of the PCP (pollen coat protein) family of proteins, some members of which have been shown to interact with SLG. In this work, we identified the SP11 gene from three additional S haplotypes and further characterized the gene. We found that (i) SP11 showed an S haplotype-specific sequence polymorphism; (ii) SP11 was located in the immediate flanking region of the SRK gene of the four S haplotypes examined; (iii) SP11 was expressed in the tapetum of the anther, a site consistent with sporophytic control of Brassica SI; and (iv) recombinant SP11 of the S(9) haplotype applied to papillar cells of S(9) stigmas, but not of S(8) stigmas, elicited SI response, resulting in inhibition of hydration of cross-pollen. All these results taken together strongly suggest that SP11 is the pollen S determinant in SI.
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PMID:The pollen determinant of self-incompatibility in Brassica campestris. 1067 56

Proline-rich tyrosine kinase 2 (Pyk2) (also known as RAFTK, CAKbeta or CADTK) has been identified as a member of the focal adhesion kinase (FAK) family of protein-tyrosine kinases and it has been suggested that the mode of Pyk2 activation is distinct from that of FAK. In the present study we investigated the mode of Pyk2 activation in human platelets. When platelets were stimulated with thrombin, Pyk2, as well as FAK, was markedly tyrosine-phosphorylated, in a manner mostly dependent on alphaIIbbeta3 integrin-mediated aggregation. The residual Pyk2 tyrosine phosphorylation observed in the absence of platelet aggregation was completely abolished by pretreatment with BAPTA/AM [bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid acetoxymethyl ester]. The Pyk2 phosphorylation was inhibited by protein kinase C (PKC) inhibitors at concentrations that inhibited platelet aggregation. In contrast, direct activation of PKC with the active phorbol ester PMA induced the tyrosine phosphorylation of Pyk2 and FAK but only when platelets were fully aggregated with the exogenous addition of fibrinogen (the ligand for alphaIIbbeta3 integrin). Furthermore, PMA-induced Pyk2 (and FAK) tyrosine phosphorylation was also observed when platelets adhered to immobilized fibrinogen. The activation of the von Willebrand factor (vWF)--glycoprotein Ib pathway with botrocetin together with vWF failed to induce Pyk2 (and FAK) tyrosine phosphorylation. Most Pyk2 and FAK was present in the cytosol and membrane skeleton fractions in unstimulated platelets. When platelets were stimulated with thrombin, both Pyk2 and FAK were translocated to the cytoskeleton in an aggregation-dependent manner. In immunoprecipitation studies, Pyk2, as well as FAK, seemed to associate with Shc through Grb2. With the use of glutathione S-transferase fusion proteins containing Shc-SH2, Grb2-SH2, and Grb2 N-terminal and C-terminal SH3 domains, it was implied that the proline-rich region of Pyk2 (and FAK) binds to the N-terminal SH3 domain of Grb2 and that the phosphotyrosine residue of Shc binds to the SH2 domain of Grb2. Although Pyk2 and FAK have been reported to be differentially regulated in many cell types, our results suggest that, in human platelets, the mode of Pyk2 activation is mostly similar to that of FAK, in terms of alphaIIbbeta3 integrin-dependent and PKC-dependent tyrosine phosphorylation. Furthermore, Pyk2, as well as FAK, might have one or more important roles in post-aggregation tyrosine phosphorylation events, in association with the cytoskeleton and through interaction with adapter proteins including Grb2 and Shc.
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PMID:Involvement of proline-rich tyrosine kinase 2 in platelet activation: tyrosine phosphorylation mostly dependent on alphaIIbbeta3 integrin and protein kinase C, translocation to the cytoskeleton and association with Shc through Grb2. 1074 87

Within the large Brassica S gene family, SLG (S locus glycoprotein) and SRK (S locus receptor kinase) participate to the control of pollen-stigma self-incompatibility. In the self-compatible species maize, S gene family members are predominantly expressed in vegetative organs but are also expressed to a lesser extent in the stigma (silk). To determine if the expression of any S gene family members correlates with female receptivity, we analyzed their expression in developing maize silks. We show that a large family of maize S transcripts is expressed in developing silks. Surprisingly, we isolated a cDNA complementary to a large portion of the antisense strand of the maize receptor kinase S domain. Rapid amplification of cDNA ends (RACE)-polymerase chain reaction, RNase protection, and Northern hybridization with single-stranded riboprobes confirmed that natural antisense S transcripts exist in leaves and seedling shoots and in all sexual tissues tested except mature pollen. These natural antisense S transcripts co-exist with several less abundant sense S transcripts. The accumulation of sense and antisense S transcripts is differentially regulated during pollen and silk development. Thus, these results support a role for S gene family members in sexual tissue development and/or compatible pollination and reveal a new level of complexity in the regulation and function of the S gene family in maize.
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PMID:Multiple S gene family members including natural antisense transcripts are differentially expressed during development of maize flowers. 1082 36

alpha v beta 3 integrins have been implicated in regulating vascular healing in animal models of arterial injury. Because the specific cellular events mediated by alpha v beta 3 integrins are not completely understood, we examined alpha v beta 3 integrin-dependent cytoplasmic events in cultured human smooth muscle cells (SMC) following treatment with thrombospondin-1 (TSP), a glycoprotein concentrated at sites of blood vessel injury. TSP treatment elicited a time-dependent association of nonmuscle myosin heavy chain-A (NMHC-A) with alpha v beta 3 integrins. NMHC-A also associated with focal adhesion kinase (FAK) in TSP-treated SMC. FAK, a nonreceptor kinase implicated in integrin-mediated signaling, was phosphorylated on tyrosine in growth-arrested SMC, but levels of tyrosine phosphorylation increased following treatment with TSP. To test whether NMHC-A was regulated by vascular injury, we examined expression in baboon brachial arteries. In uninjured arteries, NMHC-A staining was present in the media. In arteries injured by balloon withdrawal, medial NMHC-A expression was increased with intense staining at specific sites. In summary, heteromeric protein complexes involving alpha v beta 3 integrins, NMHC-A, and FAK form following treatment of human SMC with TSP. These results suggest that the formation of protein signaling complexes is one mechanism whereby alpha v beta 3 integrins influence intracellular signaling pathways.
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PMID:Protein complexes involving alpha v beta 3 integrins, nonmuscle myosin heavy chain-A, and focal adhesion kinase from in thrombospondin-treated smooth muscle cells. 1082 99

The expression of the difucosyl-lactosamine type 2 oligosaccharide Lewis Y (LeY) on peripheral blood cells was investigated. As assessed by the reactivity with the mouse anti-LeY monoclonal antibody (mAb) ABL 364 among circulating blood cells, the expression of the LeY oligosaccharide was uniquely restricted to granulocytes. Although the density of LeY expressed on resting granulocytes was weak, in vitro activation of granulocytes with fMLP induced a rapid and pronounced increase in granulocyte LeY expression. Analysis of CEA-related glycoproteins immunoprecipitated with anti-CD66 mAbs followed by immunoblotting with mAb ABL 364 showed that granulocyte LeY is attached to members of the CD66 cluster, in particular to the 160/90 kD glycoprotein recognized by anti-CD66 mAb CBL/gran 10. The activation-associated increase in LeY attached to CD66 adhesion molecules implicates a role of the LeY determinant in the cytoadhesive properties of granulocytes.
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PMID:Activation-dependent expression of the blood group-related lewis Y antigen on peripheral blood granulocytes. 1103 72

It has been suggested that the early response was a critical regulator of the remaining quiescent liver cells reentering the cell cycle after partial hepatectomy. The identification of genetic factors and function important in the early response phase during liver regeneration after partial hepatectomy will help in understanding the underlying molecular mechanisms of hepatic injuries. Through the application of complementary DNA representational difference analysis (RDA), we have identified genes that are up-regulated in early response phase during liver regeneration. Results from slot blot and Northern blot analysis confirmed that the RDA products were truly differentially expressed. In addition to well-characterized up-regulated genes during liver regeneration, including IGFBP-1, LRF-1, and metallothionein, we demonstrate the differential expression of at least 6 genes previously not known to be associated with liver regeneration. PC3 and TEC genes were identified as immediate-early response genes and were dramatically increased following partial hepatectomy. Ribosomal protein L6, ribosomal protein S7, chaperonin 10, and cytochrome oxidase I were identified to be up-regulated 4- to 5-fold after 70% partial hepatectomy. In addition to the known genes, 7 novel genes were isolated. Among them, two genes showed their up-regulation in liver regeneration by Northern blot analysis. One was exclusively expressed in liver, and no expression was observed in other tissues. Peak expression, 30-fold above baseline, occurred 60 min after 70% hepatectomy. Cycloheximide pretreatment could not suppress the induction of this gene, indicating that this gene as a novel immediate-early response gene following partial hepatectomy. The novel gene, which was represented three times in the differential clones, may be one of the highly up-expressed genes in regenerating liver. Its transcript is undetectable in normal liver; its level of mRNA increased by 0.5 h after 2/3 partial hepatectomy, reaching a maximum at 2 h. This gene is similar to human alpha-1-beta-glycoprotein (40%). These results suggest a role of these genes in the early response phase of liver regeneration.
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PMID:Identification and characterization of differentially expressed genes in the early response phase during liver regeneration. 1109 37


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