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

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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)

Recently, the SRC-like non-receptor protein tyrosine kinase p56-LCK has been shown to physically associate with the interleukin-2 receptor (IL-2-R) complex and to undergo rapid elevations in its tyrosine kinase activity upon stimulation of T lymphocytes with IL-2. The functional significance of p56-LCK kinase activation for IL-2-mediated lymphocyte responses, however, has never been directly assessed. Using gene transfer approaches, we have achieved markedly elevated levels of p56-LCK kinase activity in the IL-2-dependent cytolytic T-cell line CTLL-2 and the helper line HT-2. CTLL-2 and HT-2 cells that were stably transfected with expression plasmids encoding either the normal human p56-LCK or a constitutively active version of the mouse p56-LCK kinase (LCK[Y505]) contained striking elevations in the levels of tyrosine phosphorylation on several proteins (34-36, 50-60, 62-68, 77-78, 104-110 kDa), as determined by immunoblot analysis using anti-phosphotyrosine antibodies. CTLL-2 and HT-2 LCK- and LCK(Y505F)-transfected cells remained dependent on IL-2 for their growth and survival in culture despite the findings that (i) IL-2 specifically stimulated elevations in the activity of the endogenous p56-LCK in untransfected CTLL-2 cells without affecting the activities of the other SRC-like kinases in these cells (p59-FYN, p62-YES) and that (ii) IL-2-mediated regulation of p56-LCK correlated with IL-2-driven proliferation of these T cells. Specifically, no elevation in the proliferation (DNA synthesis) or growth of these T cells was found at any of the concentrations of IL-2 examined (0.01-25 U/ml), relative to untransfected and control transfected cells. Furthermore, when cultured in the absence of IL-2, transfected T cells whose relative levels of p56-LCK activity were elevated by approximately 20-50-fold died with the same kinetics as control cells and underwent apoptosis, as defined by uptake of trypan blue dye and DNA fragmentation assays, respectively. Taken together, these data indicate that while IL-2 can up-regulate the enzymatic activity of p56-LCK, elevated levels of p56-LCK tyrosine kinase activity are insufficient to stimulate IL-2-mediated pathways required for T-cell growth and survival. These findings thus imply the existence of other signal-transducing molecules, besides p56-LCK, that physically participate in IL-2R complexes and that are necessary for initiation of the biochemical events ultimately responsible for IL-2's pleiotropic actions on lymphocytes.
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PMID:Gene transfer investigations of p56-LCK function in IL-2-dependent T-cell lines: implications for mechanisms of IL-2-signal transduction. 129 28

Recently we described the establishment in culture and the immunophenotypic and functional characteristics of a human T-leukemia line TALL-103/2 derived from the T-cell receptor (TCR)-gamma/delta subset of T-lymphocytes. TALL-103/2 cells are absolutely dependent on interleukin 2 (IL-2) for their growth and survival in culture and thus provide a model cell line for studies of IL-2 signal transduction in a TCR-gamma/delta T-cell. In this report, we focus on the regulation of SRC-family protein tyrosine kinases (PTKs) by IL-2. TALL-103/2 cells were found to contain p56-LCK, p59-FYN, p62-YES and p53/56-LYN. Stimulation of growth factor-deprived TALL-103/2 cells with IL-2, however, induced increases in the relative activity only of the p56-LCK kinase. This IL-2-mediated increase in LCK kinase activity was manifested both by increased kinase autophosphorylation and by increased phosphorylation of the exogenous substrate enolase during in vitro kinase assays. Furthermore, immunoblot assays determined that the levels of p56-LCK protein were unaltered by IL-2-treatment, indicating that the measured elevations in LCK kinase activity reflected an increase in the specific activity of this PTK. In TALL-103/2 cells, IL-2 stimulated concentration-dependent increases in p56-LCK activity that displayed rapid and transient kinetics: detectable increases occurred within 1 minute after IL-2 stimulation, peaked at 10 minutes, and declined to baseline levels by 30 minutes. Treatment of TALL-103/2 cells with IL-4 abrogated IL-2-initiated proliferation, but did not inhibit IL-2-mediated activation of p56-LCK.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interleukin 4 inhibits IL-2-induced proliferation of a human T-leukemia cell line without interfering with p56-LCK kinase activation. 142 Sep 98

Unlike many other growth factor receptors, the known subunits of the receptors for the Interleukins IL-2 and IL-3 lack intrinsic tyrosine kinase activity, and yet increases in the phosphorylation of proteins on tyrosines is a rapid event in hematolymphoid cells following stimulation with these lymphokines. Here we show that IL-2 and IL-3 regulate the activity of specific members of the SRC-family of non-receptor protein tyrosine kinases (PTKs). In IL-2-dependent T-cell lines, IL-2 induced rapid and transient increases in the activity of the p56-LCK kinase without influencing the activities of other SRC-like PTKs (p59-FYN, p62-YES) in these T-lymphocytes. In contrast to IL-2's effects on p56-LCK in T-cells, studies of an IL-2-responsive cell line of the B-cell lineage that lacks p56-LCK revealed that IL-2 specifically regulates the activity of the p53/56-LYN kinase. Thus, some flexibility exists in the ability of various SRC-like PTKs to functionally couple to IL-2 signalling pathways. In several IL-3-dependent myeloid-committed leukemic cell lines, IL-3 was found to specifically regulate the activity of the p53/56-LYN kinase without affecting the activities of other SRC-like PTKs (p59/64-HCK, p59-FYN, p62-YES) in these hematopoietic cells. This finding that p53/56-LYN can be regulated by both IL-2 in B-lineage cells and IL-3 in myeloid-committed cells demonstrates that the same SRC-family PTK can participate in signal transduction events mediated via two independent receptor systems. Taken together, our findings imply that the specific combinations of lymphokine receptors and SRC-like PTKs available for coupling with those receptors are coordinately controlled during the differentiation of hematopoietic cells.
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PMID:Regulation of SRC-family protein tyrosine kinases by interleukins, IL-2, and IL-3. 160 36

The expression of 10 protooncogenes has been quantitatively studied in liver of male rats L10 age of 1, 10.5, 22 and 37 months. It was shown that a number of specific mRNA transcripts and, therefore, the levels of expression of protooncogenes C-MYC, C-FOS, N-MYC, HA-RAS, KI-RAS, SIS, ABL, YES, MOS and MET in rat liver were constant during life span. These data are in accordance with resistance of the rat strain L10 to spontaneous hepatocarcinogenesis.
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PMID:[Proto-oncogene expression in the liver of male rats of different age]. 171 16

The expression of protein-tyrosine kinases (PTKs; ATP:protein-tyrosine O-phosphotransferase, EC 2.7.1.112) was studied in normal human lung and various tumors by PCR followed by molecular cloning and sequence analysis. Six known PTKs (YES, FGR, LYN, HCK, PDGFB-R, and CSF1-R), as well as two additional members of this enzyme family, were detected in lung. One of the newly discovered sequences appears to represent a group of cytosolic PTKs. The cDNA sequence of the second unknown PTK revealed that it is a fourth member of the fibroblast growth factor receptor family. It was therefore called TKF (tyrosine kinase related to fibroblast growth factor receptor). Among a wide variety of cells and tissues tested, including human lymphocytes and macrophages, TKF was only found expressed in lung. Apart from normal lung, TKF expression could be demonstrated in some tumors of lung origin, but also in malignancies not derived from lung tissues. As fibroblast growth factors are generally involved in a variety of functions such as mitogenesis, angiogenesis, and wound healing, the specific expression of a receptor-related gene in lung only may point to yet another special function of this group of proteins.
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PMID:Two additional protein-tyrosine kinases expressed in human lung: fourth member of the fibroblast growth factor receptor family and an intracellular protein-tyrosine kinase. 172 May 39

An src/yes-related novel gene named syn (SYN in human gene nomenclature) has been identified in the human genome on chromosome 6 and characterized by molecular cloning. Nucleotide sequence analysis of cDNA clones showed that the c-syn gene could encode a protein-tyrosine kinase that is very similar in primary structure to the v-yes and human c-src proteins. A 2.8-kilobase transcript of the c-syn gene, which differs in size from those of the c-yes, c-src, and c-fgr genes, was observed in various cell types. These results show that syn is a new member of the tyrosine kinase oncogene family.
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PMID:yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. 352 30

A large and growing body of evidence suggests that the regulation of tyrosine phosphorylation is important in the induction of axon growth. We have examined the subcellular distribution of enzymes regulating tyrosine phosphorylation in early embryonic brain, employing a preparation of isolated growth cone particles (GCPs). Because of the early developmental age and well-characterized nature of our tissue source, our GCP preparation offers some advantages over those described previously. As was found with other GCPs, our GCPs had relatively high levels of both the growth-associated protein GAP-43 and the intracellular tyrosine kinase pp60c-arc. In addition, we found that both total tyrosine kinase activity and total tyrosine phosphatase activity were concentrated two- to threefold in the GCPs relative to a neuronal membrane fraction. Two other nonreceptor tyrosine kinases, YES and FYN, were concentrated in the GCPs to a similar degree as that seen for SRC. In addition, we examined the developmental expression in brain of the three tyrosine kinases, using both a quantitative ELISA and Western blot analysis. Our results show that FYN, like SRC, reaches a peak of expression early in development, and declines thereafter. In contrast, expression of YES peaks later, and remains high in the adult brain. Immunofluorescence staining suggests that FYN is expressed both by neurons and by glia, and possibly by neuronal precursor cells. Our results implicate multiple tyrosine kinases as well as tyrosine phosphatases in growth cone function. In addition, the concentration of FYN in early embryonic growth cones combined with its early peak of expression suggests an important role for FYN in early neuronal development.
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PMID:Tyrosine phosphorylation in early embryonic growth cones. 768 39

Somatic cell hybrids containing different deleted regions of chromosome 18 derived from patients with balanced translocations or terminal deletions were used to create a deletion mapping panel. Twenty-four sequence-tagged sites (STSs) for 17 genes and 7 anonymous polymorphic DNA fragments were identified. These STSs were used to map the 24 loci to 18 defined regions of chromosome 18. Both ERV1, previously mapped to 18q22-q23, and YES1, previously mapped to 18q21.3, were found to map to 18q11.21-pter. Several genes previously mapped to 18q21 were found to be in the order cen-SSAV1-DCC-FECH-GRP-BCL2-PLANH2-tel. The precise mapping of genes to chromosome 18 should help in determining whether these genes may be involved in the etiology of specific chromosomal syndromes associated with chromosome 18. The mapping of the polymorphic loci will assist in the integration of the physical map with the recombination map of chromosome 18.
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PMID:STS map of genes and anonymous DNA fragments on human chromosome 18 using a panel of somatic cell hybrids. 844 4

The YES1 proto-oncogene was mapped previously to human chromosome band 18q21.3 by using isotopic in situ hybridization. Using yeast artificial chromosomes (YACs) as probes and fluorescence in situ hybridization, a strong signal was detected in the region corresponding to 18p11.3. Restriction digests confirmed that the YACs contained the YES1 gene and not other cross-hybridizing, protein-tyrosine kinases. In addition, these YACs were found to contain another 18p11.32 gene, thymidylate synthase. These genes were less than 50 kb apart. Collectively, these data suggest that YES1 maps to 18p11.32 rather than to 18q21.3.
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PMID:Chromosomal reassignment: YACs containing both YES1 and thymidylate synthase map to the short arm of chromosome 18. 844 16

The cosegregation of ten coding loci has been investigated, in a panel of 37 somatic cell hybrids resulting from the fusion of a hamster cell line and river buffalo lymphocytes, by use of Southern hybridization technique. Five syntenic groups, TCRB-PGY3, ASS-ABL, FUCA1P-CRYG, MBP-YES1, and CGN1-ACTA1, previously assigned to cattle as U13, U16, U17, U28, and U29 respectively, were also found to be syntenic in buffalo. Based on the extensive syntenic conservation and banding homology between cattle and river buffalo, comparative mapping predicts the localization of these syntenic groups on river buffalo Chromosomes (Chrs) :BBU7, BBU12, BBU2q, BBU22, and BBU4q respectively as they have been previously localized on cattle Chrs BTA4, BTA11, BTA2, BTA24 & BTA28.
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PMID:Synteny mapping in river buffalo. 887 91


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