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

To determine the interstrain genomic diversity and molecular phylogeny of the recently identified variants of human T-cell lymphotropic virus type I (HTLV-I) in Melanesia, we enzymatically amplified, then directly sequenced representative regions of the gag, pol, and env genes of HTLV-I strains from 10 members of four families, including one family from Papua New Guinea and three families from the Solomon Islands. When aligned and compared to a Japanese strain of HTLV-I (ATK), the Melanesian HTLV-I strains differed by 7.6 to 8.7% in the gag, 7.1 to 9.3% in the pol, and 7.3 to 8.2% in the env gene regions. Based on 931 nucleotides, the overall sequence divergence of the 10 Melanesian HTLV-I strains from HTLV-I ATK was 7.3 to 8.1% (68 to 75 base substitutions). The intrafamilial genetic heterogeneity among these virus strains was nil to 0.2%, while the interfamilial sequence variation between HTLV-I strains from the Solomon Islands and those from Papua New Guinea was 3.4 to 4.2%, and the genetic heterogeneity among virus strains from the three Solomon Islands families was 0.2 to 0.9%. Using the maximum parsimony and neighbor-joining methods, phylogenetic analysis indicated that the HTLV-I strains from Papua New Guinea and the Solomon Islands formed a monophyletic group and that the Melanesian and cosmopolitan strains of HTLV-I have evolved along two major geographically dependent lineages.
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PMID:Interfamilial and intrafamilial genomic diversity and molecular phylogeny of human T-cell lymphotropic virus type I from Papua New Guinea and the Solomon Islands. 837 32

Simian T-cell leukemia virus (STLV-I) is an oncovirus highly related to human T-cell leukemia virus type I (HTLV-I). To further examine the extent of variability, dissemination patterns, phylogeny, and evolution of these viruses, we analyzed a new STLV-I variant from a naturally infected Cercopithecus aethiops var. tantalus from the Central African Republic. Sequence analyses of its LTR, gag, pol, env, and pX (OrfII) genes indicated that this isolate, STLV-I (Tan 90), is 6% divergent from the prototype HTLV-I (ATK) and is the most divergent African STLV-I characterized to date. Our phylogenetic data indicate that southeast Asian and African STLV-I and HTLV-I strains segregated from each other thousands of years ago and that Japanese HTLV-I strains represent a relatively recent introduction of African or New World isolates. The data also indicate that interspecies transmission occurred several times on different continents over prolonged periods of time.
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PMID:Sequence and phylogenetic analyses of a new STLV-I from a naturally infected tantalus monkey from Central Africa. 839 Jul 57

Human T-cell leukemia virus type I (HTLV-I) has been associated with adult T-cell leukemia/lymphoma and the chronic neurologic disorder tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). To study the genetic structure of the virus associated with TSP/HAM, we have obtained and sequenced a partial genomic clone from an HTLV-I-positive cell line established from cerebrospinal fluid (CSF) of a Jamaican patient with TSP/HAM. This clone consisted of a 4.3-kb viral sequence containing the 5' long terminal repeat (LTR), gag, and N-terminal portion of the pol gene, with an overall 1.3% sequence variation resulting from mostly nucleotide substitutions, as compared to the prototype HTLV-I ATK-1. The gag and pol regions showed only 1.4% and 1.2% nucleotide variations, respectively. However, the U3 region of the LTR showed the highest sequence variation (3.6%), where several changes appear to be common among certain TSP/HAM isolates. Several of these changes reside within the 21-bp boundaries and the Tax-responsive element. It would be important to determine if the observed changes are sufficient to cause neurologic disorders similar to the murine leukemia virus system or simply reflect the divergent pool of HTLV-I from different geographic locations. At this time, we cannot rule out the possibility that the observed changes have either direct or indirect significance for the HTLV-I pathogenesis in TSP/HAM.
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PMID:Nucleotide sequence analysis of HTLV-I isolated from cerebrospinal fluid of a patient with TSP/HAM: comparison to other HTLV-I isolates. 845 77

PI3K was originally discovered as a lipid kinase involved in the phosphorylation of the inositol ring in position -3, leading to the synthesis of phosphatidyl-inositol-3-4 bisphosphate. The enzyme purified from rat liver is an heterodimer of two subunits of 85 and 110 KD respectively: it phosphorylates the D3 hydroxyl of phosphoinositides to produce phosphatidyl-inositol-3-phosphate. So far the function of the 3-phospho-inositide is unclear. It is likely that the entire phospholipid serves as a second messenger, since no phospholipase C has yet been found that can cleave the inositol group with a 3 phosphate residue. However the activation targets of this second messenger are still poorly known. Recently a novel/serine/theronine kinase was insolated by three groups and called differently RAC, PKB and AKT. It exhibits sequence homology with protein kinase A and C at the carboxyl terminal, whereas the aminoterminal domain has a plectrin homology. Activation of ATK is inhibited by wortmannin, a specific inhibitor of PI3K at very low concentrations. Furthermore inositol-3-phosphate can activate ATK in vitro. In addition very recently, a linkage of G-protein coupled receptors to the MAP kinase signalled pattern through PI3K has been discovered. But what is downstream of this pathway? 70S6 kinase is an attractive candidate since this kinase, involved in protein synthesis, is activated by AKT in vivo. Interestingly AKT is the cellular protooncogene of v-ATK and this implies that ATK induces a pathway of oncogenic transformation. AKT is inhibited by dominant negative mutants of ras and thus involved in the ras-raf-MAP kinase pathway. The role of PI3K is still indefinite but it must have a paramount importance in cell signalling since nearly all growth factor receptors recruit this enzyme and that the activity of fundamental growth factor receptors like PDGF, EGF and insulin are blocked by the specific inhibitor wortmannin, leading to the conclusion that the PI3K signal is much important in mitogenesis, protein synthesis, membrane ruffling, cell transformation and cell cycle progression.
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PMID:PI3K signal and DNA repair: a short commentary. 926 40

Mutations in the Bruton's tyrosine kinase (BTK) gene result in XLA. Despite the large numbers of BTK mutations reported, no correlation can be made between the clinical phenotype and the gene defects. Analysis of Btk protein expression and activity in individuals with XLA was performed to characterize the relationship between a particular mutation, the resultant Btk protein and the clinical phenotype. In most patients studied, including those with atypical phenotypes, there was complete absence of protein expression and activity. Furthermore, in two undiagnosed individuals with a clinical phenotype suggestive of XLA, lack of protein expression was used to confirm an abnormality in Btk. These results underline the importance of protein analysis prior to speculating on protein structure and function based on the gene mutation. Lack of Btk expression in atypical phenotypes suggests that there is redundancy in B lymphocyte signalling such that alternative signalling molecules, or mechanisms, can compensate for the lack of Btk. We also suggest that analysis of Btk expression can be used as an indicator of XLA. These rapid assays may be used to screen a wider spectrum of individuals with humoral immunodeficiency in order to characterize fully the extent of Btk deficiency.
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PMID:Bruton's tyrosine kinase expression and activity in X-linked agammaglobulinaemia (XLA): the use of protein analysis as a diagnostic indicator of XLA. 948

Transmission of zucchini yellow mosaic virus (ZYMV) by aphids was examined by introducing mutations within the highly conserved proline-threonine-lysine (PTK) motif of the helper component proteinase (HC-Pro) using a cDNA full-length clone. Replacement of proline by alanine (ATK) in the PTK motif abolished transmission almost completely both from plants and from membranes. Substitution of the basic lysine by glutamic acid (PTE) did not reduce the rate of transmission compared with the wild-type. Replacement of threonine by valine (PVK) or serine (PSK) resulted in a rate of transmission that was lower than that of the wild-type. The rate was lower for PSK than for PVK. Western blot comparison did not permit attribution of HC-Pro functionality in transmission to its level in the host. The HC-Pro of strains that effected transmission (with the wild-type PTK motif, and with the mutated PTE and PVK motifs) could also bind in vitro to virions of ZYMV. HC-Pro with a PSK motif, which was less effective in assisting transmission, could bind only weakly to virions, while HC-Pro of the almost non-transmissible strains (with PAK and ATK motifs) did not bind at all. Interestingly, positive binding was recorded for transmission-defective ZYMV-Ct, which has a PTK motif but has glutamic acid instead of lysine in the lysine-leucine-serine-cysteine (KLSC) motif. These findings support the 'bridge hypothesis', and confirm the binding of the HC-Pro to the virion. The possible role of the PTK and KLSC motifs in binding to the virus and to the mouthparts of the aphid is discussed.
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PMID:Mutations in the HC-Pro gene of zucchini yellow mosaic potyvirus: effects on aphid transmission and binding to purified virions. 956 86

We studied the presence of tax and ltr genes from human T-cell lymphotropic virus type I (HTLV-I) provirus in the peripheral blood mononuclear cells from 15 seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy by PCR. Only a region of the tax gene from 10 patients was amplified. The nucleotide homologies of six Chilean isolates to the ATK-1 clone ranged between 98.7 and 99.4%.
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PMID:Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in 10 Chilean seronegative patients with tropical spastic paraparesis or HTLV-I-associated myelopathy. 962 Apr 31

Mutations in Bruton's tyrosine kinase (Btk) result in the B cell immunodeficiencies XLA in humans and Xid in mice. Both the maintenance of peripheral B cell numbers and their response to B cell antigen receptor (BCR) crosslinking depend on Btk. Btk integrates signals from multiple cell surface receptors, including BCR and G-protein coupled receptors. These Btk dependent signals control B cell proliferation and survival by mediating Ca2+ flux, activating JNK and p38 and inducing cell cycle regulatory genes.
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PMID:Btk function in B cell development and response. 969 87

Bruton's tyrosine kinase (Btk) is a non-receptor protein tyrosine kinase (PTK) that is expressed in all haemopoietic lineages except mature T cells and plasma cells. Despite the broad range of expression. mutations that inactivate this molecule affect primarily the development of the B-cell lineage. As a PTK, Btk could potentially be involved directly or indirectly in the processes that relate to the malignant transformation of all the cell lineages where this molecule is expressed. Previous studies have failed to demonstrate mutations in patients with B-cell origin acute lymphoblastic leukaemia (ALL). We have utilized a recently developed method that enables the rapid and convenient detection of mutations at the cDNA level, namely, the non-isotopic RNase cleavage assay (NIRCA) to analyse Btk sequences from 27 patients with different types of acute myeloid leukaemia (AML). The only alteration that we observed was a polymorphism at position 2031. This polymorphism has already been seen in previous studies. Furthermore, using the same methodology, we identified the Btk mutations in six XLA (X-linked agammaglobulinaemia) patients. Our results, although they do not exclude the involvement of Btk mutations in the development or progression of some type of AML, nevertheless suggest that such mutations do not constitute a major co-factor in the development of myeloid malignancies.
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PMID:Absence of Bruton's tyrosine kinase (Btk) mutations in patients with acute myeloid leukaemia. 975 52

Bruton's tyrosine kinase, which is encoded by the BTK gene, is a cytoplasmic protein tyrosine kinase (PTK) crucial for B-cell development and differentiation. It belongs to the Tec family of PTKs containing several domains that are characteristic of signalling molecules. In humans, mutations that disrupt the function of this gene lead to the classical XLA syndrome (X-linked agammaglobulinaemia), a primary immunodeficiency mainly characterized by lack of mature B cells as well as low levels of immunoglobulins. In contrast, animal models of this disease such as the xid mice display profoundly milder XLA phenotype. BTK phosphorylation and activation in response to engagement of the B-cell receptor (BCR) by antigen is a dynamic process whereby a variety of proteins interact with each other and recruit signalling molecules resulting in a physiological response such as B-cell proliferation and antibody production. The main players, however, that participate in the intracellular downstream cascade have not yet been identified and are therefore under intense scrutiny in several laboratories. This review discusses certain aspects of BTK activation following receptor stimulation by agonists and how this event is translated into the biochemical signals within the cell that eventually lead to nuclear responses.
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PMID:Signalling of Bruton's tyrosine kinase, Btk. 1007 13


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