Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using differential display, we isolated DDC-4, a secreted frizzled-related protein (sFRP), which is induced in the physiological apoptosis of hormonally regulated, reproductive tissues such as mammary gland, prostate, corpus luteum and uterus. The role of this gene in apoptosis was studied in animals overexpressing ectopic DDC-4/sFRP-4. Transgenic mice bearing the DDC-4/sFRP-4 cDNA under the control of the MMTV-LTR promoter showed lactational insufficiency and many apoptotic cells in the alveoli between day 19 of pregnancy and day 4 of lactation as demonstrated by TUNEL reaction and the presence of activated caspase-3. We performed a PKB/Akt kinase assay and studied several of its substrates using phosphorylation-specific antibodies to show reduced phosphorylation in PKB/Akt itself, as well as in glycogen synthetase kinase-3beta (GSK-3beta), BAD, and Forkhead. Taken together, our results show a role for DDC-4/sFRP-4 in abrogating an epithelial cell survival pathway at the onset of mammary gland involution.
...
PMID:Role of DDC-4/sFRP-4, a secreted frizzled-related protein, at the onset of apoptosis in mammary involution. 1272 51

Previously, we reported that glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) was a novel target for prolactin (PRL) in the mouse mammary gland. However, the signaling pathway by which PRL regulates GlyCAM 1 expression has not been specified. In the present study, we showed that PRL induced GlyCAM 1 expression in primary mammary epithelial cells of mice through the Janus kinase 2/signal transducer and activator of transcription 5 (Stat5) pathway. Deletion and site-directed mutagenesis analyses of the GlyCAM 1 promoter demonstrated that the two tandemly linked Stat5 binding sites [interferon-gamma-activated sequence 1 and -2 (GAS1 and GAS2)] in the proximal promoter region were crucial and synergistically responded to PRL. GAS2, a consensus GAS site, was essential and, by itself, weakly responded to PRL, whereas GAS1, a nonconsensus site, failed to respond to PRL but was indispensable for the maximal activity of the GlyCAM 1 promoter. Gel shift assays showed that probe containing GAS1 and GAS2 bound two Stat5 complexes, which represent Stat5 dimer and tetramer, respectively, while GAS2, by itself, bound Stat5 as a dimer only, and GAS1 showed no apparent binding activity. Interruption of tetramer formation by mutation of a tryptophan to alanine (W37A), and a leucine to serine (L83S) in the N terminus of Stat5A attenuated the synergistic effect between the two tandemly linked GAS sites. Overexpression of W37A and L83S mutants in primary mammary epithelial cells suppressed endogenous GlyCAM 1 expression.
...
PMID:Two tandemly linked interferon-gamma-activated sequence elements in the promoter of glycosylation-dependent cell adhesion molecule 1 gene synergistically respond to prolactin in mouse mammary epithelial cells. 1286 89

Antibodies to simian T-cell lymphotropic virus (STLV) were found in serum or plasma from 12 of 23 (52.2 %) gelada baboons (Theropithecus gelada) captive in US zoos. A variety of Western blot (WB) profiles was seen in the 12 seroreactive samples, including human T-cell lymphotropic virus (HTLV)-1-like (n=5, 41.7 %), HTLV-2-like (n=1, 8.3 %), HTLV-untypable (n=4, 33.3 %) and indeterminate (n=2, 16.6 %) profiles. Phylogenetic analysis of tax or env sequences that had been PCR amplified from peripheral blood lymphocyte DNA available from nine seropositive geladas showed that four were infected with identical STLV-1s; these sequences clustered with STLV-1 from Celebes macaques and probably represent recent cross-species infections. The tax sequences from the five remaining geladas were also identical and clustered with STLV-3. Analysis of the complete STLV-3 genome (8917 bp) from one gelada, TGE-2117, revealed that it is unique, sharing only 62 % similarity with HTLV-1/ATK and HTLV-2/Mo. STLV-3/TGE-2117 was closest genetically to STLV-3 from an Eritrean baboon (STLV-3/PH969, 95.6 %) but more distant from STLV-3s from red-capped mangabeys from Cameroon and Nigeria (STLV-3/CTO-604, 87.7 %, and STLV-3/CTO-NG409, 87.2 %, respectively) and Senegalese baboons (STLV-3/PPA-F3, 88.4 %). The genetic relatedness of STLV-3/TGE-2117 to STLV-3 was confirmed by phylogenetic analysis of a concatenated gag-pol-env-tax sequence (6795 bp). An ancient origin of 73 628-109 809 years ago for STLV-3 was estimated by molecular clock analysis of third-codon positions of gag-pol-env-tax sequences. LTR sequences from five STLV-3-positive geladas were >99 % identical and clustered with that from a Papio anubisxP. hamadryas hybrid Ethiopian baboon, suggesting a common source of STLV-3 in these sympatric animals. LTR sequences obtained 20 years apart from a mother-infant pair were identical, providing evidence of both mother-to-offspring transmission and a high genetic stability of STLV-3. Since STLV-3-infected primates show a range of HTLV-like WB profiles and have an ancient origin, further studies using STLV-3-specific testing are required to determine whether STLV-3 infects humans, especially in regions of Africa where STLV-3 is endemic.
...
PMID:Identification in gelada baboons (Theropithecus gelada) of a distinct simian T-cell lymphotropic virus type 3 with a broad range of Western blot reactivity. 1476 8

The aryl hydrocarbon receptor (AhR) is an intracellular receptor protein that regulates gene transcription in response to both man-made and natural ligands. A modular transactivaton domain (TAD) has been mapped to the 304 C-terminal amino acids and consists of acidic, Q-rich, and P/S/T-rich subdomains. We have used steady-state intrinsic tryptophan fluorescence and circular dichroism spectroscopy to investigate the conformation of the acidic Q-rich region. The results reveal that this region of the protein is structurally flexible but adopts a more folded conformation in the presence of the natural osmolyte trimethylamine N-oxide (TMAO) and the solvent trifluoroethanol (TFE). In protein-protein interaction studies, the acidic Q-rich region bound to components of the general transcription machinery [TATA-binding protein (TBP), TAF4, and TAF6] as well as the coactivator proteins SRC-1a and TIF2. The binding site for TBP mapped to the acidic subdomain, while SRC-1a bound preferentially to the Q-rich sequence. Significantly, the binding of TBP was modulated by induced folding of the TAD with TMAO. The results indicate that the AhR TAD makes multiple interactions with the transcriptional machinery and protein conformation plays a critical role in receptor function. Taken together, these findings support a role for protein folding in AhR action and suggest possible mechanisms of receptor-dependent gene activation.
...
PMID:Induced alpha-helix structure in the aryl hydrocarbon receptor transactivation domain modulates protein-protein interactions. 1564

Bruton's tyrosine kinase (Btk) plays critical roles in B cell development and activation. Mutations of Btk cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency in mice. An Src homology domain 2-kinase linker region exists in all Src, Abl, ZAP70/Syk and Btk/Tec non-receptor tyrosine kinase families. Missense mutations in the Btk linker region can cause XLA, supporting an essential role for this protein segment. We investigated the regulatory role of the linker region in Btk function by mutational analysis. XLA-causing mutations L369F and R372G abolished Btk-mediated calcium response without affecting Btk protein stability and kinase activity significantly. Although mutation of a well-conserved tryptophan (W260A) in the linker region of the Src family kinase Hck has been shown to cause a hyperactive kinase, an analogous mutation in Btk (W395A) dramatically decreased Btk kinase activity. Tyrosine phosphorylation in the linker region was previously shown to regulate the function of Abl and ZAP70/Syk kinases. Even though tyrosine phosphorylation was detected on tyrosine 375 in the Btk linker region, no significant alteration was observed in Btk-signaling activity and biological function when this tyrosine was mutated in DT-40 cells or in Y375F knock-in mice. Our data and previous studies suggest that each cytoplasmic tyrosine kinase family has evolved a unique strategy to utilize the linker region to regulate the function of the enzyme.
...
PMID:Mutational analysis of the SH2-kinase linker region of Bruton's tyrosine kinase defines alternative modes of regulation for cytoplasmic tyrosine kinase families. 1629 52

A 5-yr-old Caucasian boy with a new mutation in Bruton's tyrosine kinase (BTK) is described. Full sequencing of the BTK gene revealed a point mutation in exon 17 resulting in an amino acid change from tryptophan to serine at location 581 of the tyrosine kinase domain. Clinically the child presented with chronic gingivitis and had no prior history of bacterial infections. Whereas serum immunoglobulin M (IgM) levels were undetectable, IgG levels were in the low normal range. The gingivitis completely resolved after intravenous immunoglobulin therapy. Lymphocyte phenotyping revealed 0.05% B cells in his peripheral blood, which were IgG(-), IgM(+), IgD(+), CD38(+), CD20(+), CD27(-). However, 40% of the B cells also expressed CD5. This subpopulation of B cells has not previously been described in X-linked agammaglobulinaemia (XLA) patients. We suggest that the occurrence of CD5(+) B cells could correlate with a late onset and mild clinical presentations of XLA.
...
PMID:Chronic gingivitis in a new BTK mutation. 1640 41

The hepatitis B virus (HBV) envelope proteins have the ability to assemble three types of viral particles, (i) the empty subviral particles (SVPs), (ii) the mature HBV virions, and (iii) the hepatitis delta virus (HDV) particles, in cells that are coinfected with HBV and HDV. To gain insight into the function of the HBV envelope proteins in morphogenesis of HBV or HDV virions, we have investigated subdomains of the envelope proteins that have been shown or predicted to lie at the cytosolic face of the endoplasmic reticulum membrane during synthesis, a position prone to interaction with the inner core structure. These domains, referred to here as cytosolic loops I and II (CYL-I and -II, respectively), were subjected to mutagenesis. The mutations were introduced in the three HBV envelope proteins, designated small, middle, and large (S-HBsAg, M-HBsAg, and L-HBsAg, respectively). The mutants were expressed in HuH-7 cells to evaluate their capacity for self-assembly and formation of HBV or HDV virions when HBV nucleocapsid or HDV ribonucleoprotein, respectively, was provided. We found that SVP-competent CYL-I mutations between positions 23 and 78 of the S domain were permissive to HBV or HDV virion assembly. One mutation (P29A) was permissive for synthesis of the S- and M-HBsAg but adversely affected the synthesis or stability of L-HBsAg, thereby preventing the assembly of HBV virions. Furthermore, using an in vitro infection assay based on the HepaRG cells and the HDV model, we have shown that particles coated with envelope proteins bearing CYL-I mutations were fully infectious, hence indicating the absence of an infectivity determinant in this region. Finally, we demonstrated that the tryptophan residues at positions 196, 199, and 201 in CYL-II, which were shown to exert a matrix function for assembly of HDV particles (I. Komla-Soukha and C. Sureau, J. Virol. 80:4648-4655, 2006), were dispensable for both assembly and infectivity of HBV virions.
...
PMID:Analysis of the cytosolic domains of the hepatitis B virus envelope proteins for their function in viral particle assembly and infectivity. 1702 Sep 42

We report the molecular and epidemiological characterization of 128 human T cell lymphotropic virus type 1 (HTLV-1) isolates from Brazilian patients with different clinical manifestations of the infection. Thirty-two percent of the patients were asymptomatic, 44% had HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and 23% had adult T cell leukemia/lymphoma (ATLL). Phylogenetic analysis performed using part of the LTR region of the viral genome revealed that all Brazilian isolates belonged to the Cosmopolitan subtype, with the following distribution within the Transcontinental subgroup: 81.6% within the Latin American cluster and 15.8% outside the Latin American cluster. Two isolates belonged to the Japanese subgroup. Molecular analysis of the tax region showed a high nucleotide similarity ( approximately 99%) with 41 prototype sequences, including the ATK-1 isolate. The mean number of nucleotide substitutions ranged from 1 to 8. Five specific nucleotide substitutions, C7401T, T7914C, C7920T, C7982T, and G8231A, were highly conserved among the Brazilian isolates (79.6%), with a frequency ranging from 81.6% to 100% in the sample group and from 18.4% to 24.1% in the prototypes used, suggesting the existence of a molecular signature. These changes were not correlated with a specific clinical status of the patients and could be a molecular characteristic of the HTLV-1 strains that circulate in Brazil.
...
PMID:Distribution of human T cell lymphotropic virus type 1 (HTLV-1) subtypes in Brazil: genetic characterization of LTR and tax region. 1706 64

Melatonin is an effective antioxidant, immunostimulant, gonadal maturating regulator and antistress indoleamine that may be potentially useful for fish farmers. We have explored two possible ways of increasing plasma melatonin levels through the diet: direct melatonin supplementation (ME diet) and supplementation with the melatonin precursor tryptophan (TRP diet). To this end, a group of sea bass was fed a commercial diet (STD diet) at a regular time for 16 days, after which plasma, intestine, and bile samples were taken at four different time points: 120 min before, and 15, 180 and 480 min after feeding. Locomotor activity, intestinal and biliary melatonin, and plasma melatonin, serotonin and cortisol levels were measured. This same sampling process and analyses were also carried out after feeding sea bass TRP diet or ME diet for 1 week. Our results show that melatonin, but not tryptophan supplementation of the diet increases plasma, intestine and bile levels of melatonin. Plasma serotonin levels, on the other hand, were increased by dietary tryptophan, but not by melatonin, confirming the availability of supplemented tryptophan for serotonin synthesis. Both treatments were equally effective in reducing the high cortisol levels observed with the STD diet.
...
PMID:Response of plasma and gastrointestinal melatonin, plasma cortisol and activity rhythms of European sea bass (Dicentrarchus labrax) to dietary supplementation with tryptophan and melatonin. 1712 89

PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.
...
PMID:Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6. 1782 67


<< Previous 1 2 3 4 5 6 7 8 Next >>

---