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)

Nephron functions of an improved isolated perfused rat kidney preparation were studied by micropuncture techniques. Single-nephron glomerular filtration rate (SNGFR), intratubular pydrostatic pressures (IP), transit time (TT), and the reabsorption (R) of H2O, Na, Cl, and K were measured in superficial proximal (PT) and distal tubules (DT) of the preparation. Mean SNGFR was 27.2 nl/min and 25.2 nl/min when measured in PT and DT, respectively. The PT transport functions were well maintained throughout the perfusion (mean values were: IP, 14.3 mmHg; TT, 17.7 s; fractional (F) RH2O, 64%; absolute RH2O, 15.4 nl/min; FRNA, 66.5%; FRK, 71%, and tubular fluid-to-perfusate tf/p) ratio of Cl, 1.37). The short loops of Henle reabsorbed less than 10% of the load of H2O and Na delivered to them and the TF/P ratio of electrolytes in the earliest DT segments were high (TF/P)Na = 0.88, (TF/P)Cl = 1.27, and (TF/P)K = 1.11). This deficiency in function of Henle's loop explains, at least in part, the degree of natriuresis of the preparation (overall FRNa = 97.5%). Transit time to end DT was prolonged (82.3 S) and IP in DT elevated (14.9 mmHg). The DT was able to compensate, in part, for the overload from Henle's loop by reabsorbing 36% of the fluid load and 54% of the Na load delivery to it. We concluded that the improved isolated perfused rat kidney is a suitable preparation with which to study several aspects of renal function, particularly proximal tubules transport functions.
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PMID:Nephron function of the isolated perfused rat kidney. 99 Jan 8

We report the cloning of a novel tyrosine kinase (TyK)-encoding gene (TYK) from the human hepatoma cell line Hep3B. Using the polymerase chain reaction (PCR) and oligodeoxyribonucleotide primers based on conserved TYK motifs, a 180-bp fragment was cloned and used to obtain full-length cDNA clones of 2.9 kb, with an open reading frame of 505 amino acids (aa). Restricted expression was detected by Northern blotting or reverse-transcribed PCR in a broad range of cell lines. The predicted aa sequence contains characteristic TyK motifs without a transmembrane region, suggesting an intracellular localization. There was 49% aa sequence identity with human FYN product and 47% with human SRC product; however, several structural differences distinguish this clone from other SRC subfamily members. This clone, FYN-related kinase or FRK, is a novel member of the intracellular TYK gene family.
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PMID:Cloning of FRK, a novel human intracellular SRC-like tyrosine kinase-encoding gene. 751 Feb 61

To identify protein tyrosine kinase (PTK) genes preferentially expressed in renal cell carcinoma cell line, we screened a PTK-cDNA-enriched library constructed from RNA of an renal cell carcinoma cell line with a PTK probe, each produced from renal cell carcinoma, gastric cancer or esophageal cancer cell lines by degenerate polymerase chain reaction. Two cDNA fragments of PTK genes, FRK and FLT-3, were isolated from the PTK-cDNA-enriched library of the renal cell carcinoma cell line by differential hybridization technique. The FRK cDNA clone represented 15.8% of the PTK-cDNA-enriched library from the renal cell carcinoma cell line, while the FLT-3 cDNA clone was 2.8% of the same library. Both of the two PTK genes were expressed preferentially in renal cell carcinoma cell lines. This method, described here, is useful for the rapid isolation of PTK cDNA fragments, including a low abundant cDNA, preferentially expressed in a specific cell line.
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PMID:Rapid isolation of cell-type-specific protein tyrosine kinases by degenerate polymerase chain reaction combined with differential hybridization technique. 766 53

A novel protein tyrosine kinase (PTK) was previously identified by us from the rat insulin-producing cell line, RINm5F, by polymerase chain reaction (PCR). By using this PCR fragment to screen a cDNA library from the mouse insulin-producing cell line beta TC-1, a cDNA clone of about 2.0 kb was obtained which encodes the entire amino acid (aa) sequence of the corresponding PTK. The deduced aa sequence reveals strong homology with the members of the SRC family of intracellular PTKs. We have designated the gene as BSK (beta-cell Src-homology tyrosine kinase). Southern blot analysis after PCR with primers specific for BSK confirmed its expression in fetal and adult islets of Langerhans, in RINm5F cells and in mouse kidney. Northern blots using poly(A)+RNA from non-beta-cell tissues showed that the BSK cDNA hybridized to three mRNA transcripts (2.9, 3.1 and 5.0 kb) present in kidney, liver and lung. Extensive homology of BSK with the recently identified human gene FRK was observed. It is concluded that Bsk is a murine Frk homologue with a specific pattern of tissue expression.
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PMID:Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution. 783 7

AP-1 is a collection of dimeric sequence specific, DNA binding, transcriptional activators composed of Jun and Fos subunits. The composition, the level and the activity of AP-1 complexes are regulated in response to extracellular stimuli. An important role in this regulation is played by mitogen-activated protein kinases (MAPKs). The specific roles of three MAPKs, namely ERK, JNK and FRK, in modulation of both the level and activity of AP-1, are discussed.
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PMID:The regulation of AP-1 activity by mitogen-activated protein kinases. 865 Feb 58

Many non-receptor protein-tyrosine kinases (PTKs) function as subunits of receptors, either receptors with or without intrinsic PTK catalytic activity of their own. There are currently at least 33 known vertebrate genes that encode non-receptor PTKs. These can be divided into nine families: Abl, Fes/Fer, Syk/Zap70, Jak, Tec, Fak, Ack, Src, and Csk. Four additional non-receptor PTKs (Rlk/Txk, Srm, Rak/Frk, and Brk/Sik) do not appear to belong to any of the defined families. Here we review current knowledge of the general roles of non-receptor PTKs, as well as the characteristic features and functions of each family and its family members.
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PMID:Vertebrate non-receptor protein-tyrosine kinase families. 914 60

Quenched fluorescence peptides were used to investigate the substrate specificity requirements for recombinant wild-type angiotensin I-converting enzyme (ACE) and two full-length mutants bearing a single functional active site (N- or C-domain). We assayed two series of bradykinin-related peptides flanked by o-aminobenzoic acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp), namely, Abz-GFSPFXQ-EDDnp and Abz-GFSPFRX-EDDnp (X = natural amino acids), in which the fluorescence appeared when Abz/EDDnp are separated by substrate hydrolysis. Abz-GFSPFFQ-EDDnp was preferentially hydrolyzed by the C-domain while Abz-GFSPFQQ-EDDnp exhibits higher N-domain specificity. Internally quenched fluorescent analogues of N-acetyl-SDKP-OH were also synthesized and assayed. Abz-SDK(Dnp)P-OH, in which Abz and Dnp (2,4-dinitrophenyl) are the fluorescent donor-acceptor pair, was cleaved at the D-K(Dnp) bond with high specificity by the ACE N-domain (k(cat)/K(m) = 1.1 microM(-)(1) s(-)(1)) being practically resistant to hydrolysis by the C-domain. The importance of hydroxyl-containing amino acids at the P(2) position for N-domain specificity was shown by performing the kinetics of hydrolysis of Abz-TDK(Dnp)P-OH and Abz-YDK(Dnp)P-OH. The peptides Abz-YRK(Dnp)P-OH and Abz-FRK(Dnp)P-OH which were hydrolyzed by wild-type ACE with K(m) values of 5.1 and 4.0 microM and k(cat) values of 246 and 210 s(-)(1), respectively, have been shown to be excellent substrates for ACE. The differentiation of the catalytic specificity of the C- and N-domains of ACE seems to depend on very subtle variations on substrate-specific amino acids. The presence of a free C-terminal carboxyl group or an aromatic moiety at the same substrate position determines specific interactions with the ACE active site which is regulated by chloride and seems to distinguish the activities of both domains.
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PMID:Peptidase specificity characterization of C- and N-terminal catalytic sites of angiotensin I-converting enzyme. 1091 58

The tyrosine kinase (TK) family includes many growth factor receptors, cell cycle regulators, and oncoproteins. Moreover, the receptor TKs HER2/neu and epidermal growth factor receptor are overexpressed in a subgroup of breast tumors and correlate with more aggressive behavior. Thus, TKs are being actively pursued as therapeutic targets. The purpose of this study was to determine the expression pattern of TKs in breast cancer. Reverse transcription-PCR was performed with degenerate primers based on conserved motifs of the catalytic domains of TKs, and the identities of the reverse transcription-PCR products were determined by digestion with a panel of restriction enzymes. Using a TK display assay, we studied the TK profiles of 13 breast cancer cell lines and two normal immortalized breast epithelial cell lines. The TK display assay reproducibly demonstrated known differences in HER-2/neu expression between cell lines. Several TKs, including receptor TKs Axl, Cak, fibroblast growth factor receptor 4, HEK8, HER2/neu, c-MET, RET, and nonreceptor TKs ARG, BRK, Janus kinase 1, Rak, and YES were detected in breast cancer cells. Several kinases were differentially expressed among the cell lines. Similar TK profiles were found using RNA from human breast tumors. We conclude that there is significant variability in the TK expression pattern of breast cancers. This variability should be considered when selecting TK inhibitors to treat patients.
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PMID:Expression profile of tyrosine kinases in breast cancer. 1183 50

The tyrosine kinases Brk/PTK6/Sik, Srm, Frk/Rak/Gtk/Iyk/Bsk, and Src42A/Dsrc41 have a low degree of sequence homology to other known kinases, including one another. We show here that the exon structure of these kinases, which we will call the Brk family, is highly conserved and distinct from each of the major families of intracellular kinases containing SH3, SH2, and tyrosine kinase domains, including c-Src and Fyn. Brk/Sik and Srm are 1.1 kb apart on human chromosome 20q13.3 and likely are the result of duplication in cis. Several Brk family kinases have an inhibitory effect on Ras pathway signaling from receptor tyrosine kinases. Members of this family can act either in the membrane or at the nucleus, and may change localization patterns depending on external stimuli. Brk has been shown to phosphorylate two proteins in vivo: Sam68. a substrate for Src in mitosis that can substitute for Rev in nuclear export of RNAs; and BKS, a novel adaptor molecule. Brk also functions as a rapid downstream signaling intermediate following calcium-induced differentiation in keratinocytes. It is possible that Brk family kinases may share common functions and interaction partners, which remain for the most part unexamined.
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PMID:Brk, Srm, Frk, and Src42A form a distinct family of intracellular Src-like tyrosine kinases. 1272 32

Recent experiments have unravelled novel signal transduction pathways that involve the SRC homology 2 (SH2) domain adapter protein SHB. SHB is ubiquitously expressed and contains proline rich motifs, a phosphotyrosine binding (PTB) domain, tyrosine phosphorylation sites and an SH2 domain and serves a role in generating signaling complexes in response to tyrosine kinase activation. SHB mediates certain responses in platelet-derived growth factor (PDGF) receptor-, fibroblast growth factor (FGF) receptor-, neural growth factor (NGF) receptor TRKA-, T cell receptor-, interleukin-2 (IL-2) receptor- and focal adhesion kinase- (FAK) signaling. Upstream of SHB in some cells lies the SRC-like FYN-Related Kinase FRK/RAK (also named BSK/IYK or GTK). FRK/RAK and SHB exert similar effects when overexpressed in rat phaeochromocytoma (PC12) and beta-cells, where they both induce PC12 cell differentiation and beta-cell proliferation. Furthermore, beta-cell apoptosis is augmented by these proteins under conditions that cause beta-cell degeneration. The FRK/RAK-SHB responses involve FAK and insulin receptor substrates (IRS) -1 and -2. Besides regulating apoptosis, proliferation and differentiation, SHB is also a component of the T cell receptor (TCR) signaling response. In Jurkat T cells, SHB links several signaling components with the TCR and is thus required for IL-2 production. In endothelial cells, SHB both promotes apoptosis under conditions that are anti-angiogenic, but is also required for proper mitogenicity, spreading and tubular morphogenesis. In embryonic stem cells, dominant-negative SHB (R522K) prevents early cavitation of embryoid bodies and reduces differentiation to cells expressing albumin, amylase, insulin and glucagon, suggesting a role of SHB in development. In summary, SHB is a versatile signal transduction molecule that produces diverse biological responses in different cell types under various conditions. SHB operates downstream of GTK in cells that express this kinase.
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PMID:The FRK/RAK-SHB signaling cascade: a versatile signal-transduction pathway that regulates cell survival, differentiation and proliferation. 1277 87


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