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)

A regional physical and transcription map involving yeast artificial chromosomes (YACs), cosmids, and cDNAs has been constructed for Xq21.3-q22 around the gene BTK (formerly atk or BPK) defective in X-linked agammaglobulinemia (XLA). With a positional cloning strategy employing direct cDNA selection, novel cDNAs were found to cluster in the region of approximately 100 kb flanking the XLA and alpha-galactosidase A loci. While these widely expressed transcripts are in the area known to contain CpG islands, a less evolutionarily conserved gene, located more than 130 kb distal of DXS178, maps to cosmid clones that could not be digested with rare-cutting restriction enzymes. The presence of transcribed sequences flanking the BTK allowed us to investigate their involvement in complex XLA phenotypes. Southern blot analysis using cDNA clones isolated from this region permitted us to exclude a contiguous deletion syndrome as an underlying defect in three patients with XLA and associated growth hormone deficiency. A single XLA patient with torsion dystonia and cosegregating X-linked deafness has been found with a deletion in the 3' part of BTK extending centromerically into the flanking expressed sequence DXS1274E. This suggests a possible involvement of the DXS1274E in this phenotype. The GenBank accession numbers for novel cDNA sequences are as follows: DXS1269E (L20773), DXS1271E (UO1923), DXS1273E (UO1925), and DXS1274E (UO1922).
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PMID:Isolation of cosmid and cDNA clones in the region surrounding the BTK gene at Xq21.3-q22. 795 28

The acoustic input impedence of the ear is a useful measure of the behavior of the middle ear and of its effect on the acoustics of the external ear. A high-impedance acoustic source with an integral microphone was designed for acoustic-impedance measurements. The source's Norton equivalent circuit was determined from measurements of the sound pressure it generated in known acoustic loads. Tests on simple acoustic configurations show errors in impedance measurements of less than 10% in magnitude and 7 degrees in angle over a frequency range from 10 Hz to 10 kHz with increasing errors at higher frequencies. Measurements at the tympanic membrane (TM) on five cat ears with widely opened middle-ear cavities show an impedance that is compliance-like below 0.3 kHz and approximately resistive above 2 kHz. With the cavities intact the impedance magnitude is somewhat larger for low frequencies, has a sharp maximum near 4 kHz, and at the highest frequencies is little affected by the state of the cavities. Impedance magnitude varies among ears by a factor of 3. The pressure reflection-coefficient that is determined from the impedance is frequency dependent with magnitude between 0.2 and 1. To characterize the motion transformation of the TM we calculate the ratio of tympanic-membrane volume velocity to the velocity of the mallear umbo, called here the kinematic area ATK. This complex quantity is constant with an angle of zero for frequencies below 0.6 kHz, but at higher frequencies both magnitude and angle of ATK vary with frequency.
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PMID:Measurements of the acoustic input impedance of cat ears: 10 Hz to 20 kHz. 796 32

X chromosome-linked agammaglobulinemia is a life-threatening disease that involves a failure in normal development of B lymphocytes and is associated with missense mutations in BTK, a gene encoding a cytoplasmic tyrosine kinase (Bruton agammaglobulinemia tyrosine kinase, EC 2.7.1.112), a member of the Tec family of protein-tyrosine kinases. The genomic organization has been determined by using conventional restriction fragment mapping, extended DNA sequencing, and PCR fragment-sizing approaches. The DNA sequences of the 18 coding exons composing BTK and their flanking-region sequences are reported; an additional exon(s) encodes a 5' untranslated segment. Single-base-pair substitutions and 4-nt deletions resulted in amino acid replacement, premature termination, frameshift, and exon deletion in a group of X chromosome-linked agammaglobulinemia patients exhibiting different clinical presentations and courses. The nature of the mutations is interpreted in terms of the genomic organization of the BTK gene and the disease course in individual patients. Several examples are found in which the same mutation occurs in unrelated patients, and one of these mutations occurs at the same codon that is substituted in the murine form of BTK, resulting in X chromosome-linked immunodeficiency disease. Considerable variation in presentation and disease course in X chromosome-linked agammaglobulinemia appears associated with the nature and position of different missense mutations.
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PMID:Genomic organization and structure of Bruton agammaglobulinemia tyrosine kinase: localization of mutations associated with varied clinical presentations and course in X chromosome-linked agammaglobulinemia. 809 Jul 69

Limited nucleotide sequences of human T-cell lymphotropic virus type I (HTLV-1) provirus isolated from the first case of a Korean patient with HTLV-I associated myelopathy and tropical spastic paraparesis (HAM/TSP) were analysed and compared with other isolates from different regions of the world. The sequences of the env, LTR regions (536bp, 690bp respectively) showed 98.7%, 99.3% homologies with the prototype HTLV-I, ATK-1, isolated from a Japanese Adult T-cell leukemia (ATL) patient. A comparison between other isolates from different geographical origins revealed that the Korean HTLV-I isolate is more closely related to Japanese isolates than to those from other geographical origins.
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PMID:Nucleotide sequence analysis of HTLV-I isolate from a Korean patient with HAM/TSP. 812 36

The region comprised between the amino acids 175 and 199 of the HTLV-I envelope surface glycoprotein is one of the immunodominant domains of this molecule. In this region, which is well recognized by sera from HTLV-I infected patients, a substitution of the proline at position 192 by a serine has been described in some isolates. Because this mutation could modify the secondary structure of the glycoprotein molecule, we studied the inference of the presence of proline or serine on the recognition of the region 175-199 by human sera. For this, three peptides have been synthetized (a 25-mer 175-199 corresponding to the sequence of the ATK prototype, and two internal 10-mer 190-Pro-199 and 190-Ser-199 having a proline or a serine at position 192) and tested by immunosorbent assay. While most sera reacted with 190-Pro-199 and with 190-Ser-199 synthetic peptides, a differential recognition was observed according to the pathology associated to HTLV-I infection. Moreover sera corresponding to patients infected with a virus harboring a serine at position 192 were found to recognize only the 10-mer with a serine. These data indicates that HTLV-I is subject to antigenic variability.
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PMID:Recognition by human sera of a variable region of the surface glycoprotein of HTLV-I. 815 6

To identify the novel receptor tyrosine kinases (RTKs) critical to the proliferation of hematopoietic stem cells, we performed polymerase chain reaction-based cloning from highly purified murine hematopoietic stem cells. Lineage marker-negative, c-KIT-positive, and Ly6A/E- or Sca-1-positive (Lin-c-KIT+Sca-1+) cells were sorted by a fluorescence-activated cell sorter. Two sets of degenerate oligonucleotide primers were directed to the conserved sequences of the catalytic domain, and were used to amplify cDNAs that encode protein tyrosine kinases (PTKs). One hundred cDNA clones were sequenced and 8 RTKs were identified, as well as 12 non-RTKs and 2 serine/threonine kinases. Sixteen cDNAs were identical to the known kinase genes (PKC beta, JAK-1, JAK-2, TYK-2, HCK, FGR, FYN, BLK, c-FES, FER, c-ABL, c-KIT, FLK-1, FLK-2, IGF1R, and ECK). Six novel cDNA sequences (stk series) were identified. However, three of them turned out to be BPK, RYK, and TEK. The remaining three showed high homology to S6 kinase II, JAK-2, and v-SEA/c-MET, respectively. Characterization of full-length cDNA sequence of the v-SEA/cMET-related gene showed that this was a novel RTK gene and we named this gene STK (stem cell-derived tyrosine kinase). We identified two distinct forms of STK cDNA; the short one encoded a putative truncated protein that lacked most of the extracellular domain. STK was expressed at various stages of hematopoietic cells, including stem cells, but we could not detect any apparent expression in other adult tissues. The expression of the truncated form of mRNA was more predominant than that of the complete form. STK was assigned by fluorescent in situ hybridization to the R-positive F1 band of chromosome 9, the same region to which hepatic growth factor-like protein has been assigned. Characterization of these PTKs, including STK, will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells.
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PMID:Molecular cloning of a novel receptor tyrosine kinase gene, STK, derived from enriched hematopoietic stem cells. 819 52

We have amplified, through PCR, the full-length tax gene of human T cell leukaemia virus type 1 (HTLV-1) derived from proviral DNA of peripheral blood lymphocytes of five first degree relatives of Afro-Caribbean origin. One patient (the father) had adult T cell leukaemia (ATL), one (the mother) tropical spastic paraparesis (TSP), and three (children) were healthy asymptomatic carriers. All five family members had identical tax nucleotide sequences as determined by direct sequencing of PCR products. This sequence was compared with tax gene sequences of an unrelated TSP patient of Afro-Caribbean origin, and of C8166 cells, and found to have one and seven nucleotide differences, respectively. At the amino acid level these three sequences differed from the HTLV-1 prototype Japanese strain (ATK-1). All sequence changes were clustered towards the 3' end of the gene. These data demonstrate the complete conservation of an HTLV-1 gene following, presumably, horizontal and vertical transmission of the virus. Clones of this gene showed more sequence variation within the TSP patient than the ATL patient, mostly consisting of point mutations; there was no conservation of mutations between the two individuals. These mutations occurred only in individual clones of the ATL patient whereas those of the TSP patient were found to be repeated in different clones. A tax-specific cytotoxic T lymphocyte response was observed in two asymptomatic carriers with low antibody titres, whereas none was detected in an individual with a high antibody level. No tax-specific sequence was identified which may have contributed to the apparently high degree of transmission from mother to children (three of five children tested) nor account for the differences between disease symptoms in the parents.
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PMID:Complete sequence conservation of the human T cell leukaemia virus type 1 tax gene within a family cluster showing different pathologies. 824 71

A study of simian T-cell lymphoma/leukemia virus infection, conducted on 747 nonhuman primates belonging to 14 different species in Central and Western Africa, indicated that 4 species (Cercopithecus aethiops, Erythrocebus patas, Papio doguera, and Cercopithecus mona pogonias) had a high prevalence of seropositivity to simian T-cell lymphoma/leukemia virus type I (STLV-I). The other nonhuman primate species, however, had negative or low levels of anti-HTLV-I antibodies. STLV-I pol and env DNA was detected in 12 of 12 different animals among the seropositive species. However, STLV-I pX DNA could be detected in only 10 of 12 animals. Comparative phylogenetic analyses based on 140 bp sequence of the pol gene indicate that these STLV-I isolates were 0-9% divergent from each other and were 3.5-7% divergent from the prototype related human retrovirus HTLV-I (ATK). The West African STLV-I isolates formed a unique phylogenetic cluster as did most of the Central African STLV-I isolates, save for STLV-I (Tan 90). The phylogenetic data indicate that cross species transmission of HTLV-I and STLV-I continued to occur long after their ancestral strain separated from the progenitor to HTLV-II. Comparative amino acid analyses indicated that there was marked conservation of the TAX protein regardless of host species, while the pol and REX proteins exhibited increasing levels of diversity.
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PMID:Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia viruses (STLV-I) from various naturally infected monkey species from central and western Africa. 825 65

Human T cell lymphotropic virus type I (HTLV-I) infection in India has been found to be associated with adult T cell leukaemia/lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) among life-long residents of southern India. To examine the heterogeneity of HTLV-I strains from southern India and to determine their relationship with the sequence variants of HTLV-I from Melanesia, 1149 nucleotides spanning selected regions of the HTLV-I gag, pol, env and pX genes were amplified and directly sequenced from DNA extracted from whole blood blotted onto filter paper and from peripheral blood mononuclear cells, obtained from one patient with HAM/TSP, two with ATLL and eight asymptomatic carriers from Andhra Pradesh, Kerala and Tamil Nadu. Sequence alignments and comparisons indicated that the 11 HTLV-I strains from southern India were 99.2% to 100% identical among themselves and 98.7% to 100% identical to the Japanese prototype HTLV-I ATK. The majority of base substitutions were transitions and silent. No frameshifts, insertions, deletions or possibly disease-specific base changes were found in the regions sequenced. The observed clustering of the Indian HTLV-I strains with those from Japan, as determined by the maximum parsimony method, suggested a common source of HTLV-I infection with subsequent parallel evolution. Amplification of DNA from blood specimens collected on filter paper may be useful for the study of other blood-borne pathogens.
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PMID:Sequence analysis of human T cell lymphotropic virus type I strains from southern India: gene amplification and direct sequencing from whole blood blotted onto filter paper. 827 90

Nucleotide sequences of two HTLV-I proviruses isolated from Indian patients with HAM/TSP were analyzed. The sequence data of the env, pX, and LTR regions showed 98-99% homologies with the prototype HTLV-I, ATK-1, isolated from a Japanese ATL patient, indicating that HTLV-I isolates in India and Japan are similar, with minor variations. However, certain small sequences of noncoding regions in the pX and LTR showed differences of 6.1 and 7.2%, respectively, thus the conclusion could vary depending on the regions and length of the sequences used for comparison.
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PMID:Limited sequence divergence of HTLV-I of Indian HAM/TSP patients from a prototype Japanese isolate. 834 93


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