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

Serum amino acid (AA) levels were determined for 18 cholecystectomy patients who had preserved and immediately utilized G-I function for absorption of 3,000 kcal/day elemental diet. Ten were given 132 gm AA/day; eight were given only 66 gm AA/day. Historical controls were 27 comparable patients who had received conventional hypocaloric intravenous (IV) regimens. Unfed patients' branched chain AAs (BCAAs) + TYR were depressed initially, then rebounded by day 3 or 4. Their glucogenic AAs were still depressed after 72 hours. Complete restoration of the basal pattern required five to ten days. Fully nourished patients maintained basal levels of all AAs on day 1. Every AA rose above basal, some with statistical significance as early as day 2. Moderately fed patients had BCAA depression, but for only 24 hours. LEU, ILE, VAL, TYR, MET, ASP, LYS, and ARG had already returned to basal levels on day 2, while the remaining AAs were much less depressed than in the unfed controls. All fed patients were discharged uneventfully 24-48 hours postcholecystectomy. The positive protein balance and elevated AA levels correlate with enhanced wound healing, host sepsis resistance, and shortened hospitalization.
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PMID:Elevation of postoperative plasma amino acid concentrations by immediate full enteral nutrition. 643 8

An enkephalin-containing peptide originating from ovine adrenal proenkephalin has been purified and sequenced. The sequence of the peptide is: GLY-GLY-GLU-VAL-LEU-GLY-LYS-ARG-TYR-GLY-GLY-PHE-MET (preproenkephalin 128-140) which represents a portion of peptide F (preproenkephalin 107-140). This peptide has a sequence identical to that of bovine preproenkephalin 128-140 while it differs from the corresponding human sequence in positions 129, 131 and 133.
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PMID:Purification and sequence of an opioid peptide derived from ovine proenkephalin. 654 17

A lot of over 60 atherosclerotics with clinical manifestations of senile depressive illness was studied comparatively with a lot of subjects of the same age with essential arterial hypertension (EAH). As concerns the behaviour of the catecholamine content in CSF and blood, the total catecholamines are approxiately equal in the two lots, but with a clear difference of the catecholamine fractions. The CSF catecholamines behaviour in old atherosclerotics is characterized by the presence of increased values of noradrenaline (NA) and of adrenaline (A), with increased statistical significance, but without modifications of the adrenaline percentage (A %) from the total catecholamines, comparatively to the values found in normal subjects. The serotonin (5-HT) content of the CSF in men with atherosclerotic senile depressive illness was lower even than in subjects with coronary atherosclerosis. In atherosclerosis protides modifications precede the histologic changes. In CSF, GLU, ALA, TYR increase in old subjects. In blood, GLU, ALA, TYR, HIS, LEU, SER increase in the same subjects. ARG decreases with age. THR is higher in men than in women. In the urine of all the men as well as of all the women of more than 60 years, GLN and ALA have increased values. LYS increases with age. GLN and ARG are higher in men than in women.
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PMID:Pattern of the cerebrospinal fluid (CSF) and blood biogenic amines and of the CSF, blood and urine amino acids as pathogenetic ground of the senile depressive illness. 677 91

Sixteen growing Alpine wethers (average BW 35 +/- 2 kg) were assigned to one of four treatments to evaluate tissue retention of the leucaena toxins mimosine (MIM) and 2,3-dihydroxypyridine (2,3-DHP). Treatments were infused i.v. for 2 d and were 1) saline control, 2) MIM (200 mg.kg BW-.75.d-1), 3) 2,3-DHP (200 mg.kg BW-.75.d-1), or 4) MIM (100 mg.kg BW-.75.d-1) + 2,3-DHP (100 mg.kg BW-.75.d-1). Immediately after the infusion, the goats were slaughtered and tissue concentrations of MIM and 2,3-DHP were determined via HPLC. No detectable levels of either toxin were found in spleen, heart, lung, or muscle; however, appreciable amounts of MIM and 2,3-DHP were found in plasma, kidney, and liver samples. Kidney MIM content was greater (P < .01) than that of liver, although liver tended to retain slightly more 2,3-DHP (P > .05). Infusion of MIM resulted in a plasma MIM content of 39 to 54 mumol/L and reduced (P < .01) plasma PHE and LEU. Infusion of 2,3-DHP resulted in a plasma 2,3-DHP content of 9.4 mumol/L and increased plasma THR, ARG, VAL, PHE, ILE, LEU, and LYS concentrations (P < .10). Humans consuming offals from ruminants consuming large amounts of the leguminous forage leucaena may be exposed to appreciable quantities of MIM and 2,3-DHP.
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PMID:Technical note: tissue residues of mimosine and 2,3-dihydroxypyridine after intravenous infusion in goats. 760 31

The clinical isolate Escherichia coli PEY was highly resistant to amoxycillin, ticarcillin and piperacillin associated to beta-lactamase inhibitors such as clavulanic acid, sulbactam, tazobactam and brobactam but susceptible to cephalosporins, aztreonam and imipenem. The susceptibility to mecillinam indicated that this phenotype was not related to hyperproduction of the TEM-1 beta-lactamase. E. coli PEY produced a new plasmid-mediated inhibitor-resistant beta-lactamase of pI 5.2, which was named IRT-4. The determination of the amino acid sequence (Swiss-Prot accession number, P00810) of the purified protein indicated that IRT-4 differed from TEM-1 by two substitutions: Leu for Met-69 (ABL numbering) and Asp for Asn-276. A Met-69-Leu variant of TEM-1, obtained by site-directed mutagenesis, has been described as resistant to clavulanate. The Asp for Asn-276 substitution has not been reported previously. The side chains of Asp-276 and Arg-244 were expected to interact. Determinations of 50% inhibitory concentrations of beta-lactamase inhibitors and substrate profile of IRT-4 suggested that such an ionic bond was implicated in the alteration of the mechanistic process of TEM-1 beta-lactamase.
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PMID:Characterization and amino acid sequence of IRT-4, a novel TEM-type enzyme with a decreased susceptibility to beta-lactamase inhibitors. 805 82

Protein kinase play important roles in the growth and differentiation of cells. We have isolated cDNA clones from the human megakaryocytic cell line CMK11-5 that encode a novel protein kinase, which we call SPRK (src-homology 3 (SH3) domain-containing proline-rich kinase). The gene sequence predicts an 847-amino acid protein kinase with a unique domain arrangement. An amino-terminal glycine-rich region is followed by an SH3 domain and a kinase domain that is similar to both tyrosine and serine/threonine kinases. Adjacent to the kinase domain are two closely spaced leucine/isoleucine zipper motifs and a stretch of basic amino acids that resembles karyophilic nuclear localization signals. The COOH-terminal half of SPRK is basic, and proline accounts for 24% of the COOH-terminal 216 amino acids. The sprk gene is widely expressed as a 4-kilobase transcript in adult and fetal human tissues. Transfection of 293 cells with a vector encoding an epitope-tagged SPRK results in the expression of a 95-kDa protein. The epitope-tagged SPRK becomes phosphorylated on serine and threonine residues in an in vitro kinase assay, whereas SPRK variants with point mutations in the predicted ATP-binding site fail to become phosphorylated. These data indicate that SPRK has serine/threonine kinase activity. The SH3 domain of SPRK is interrupted by a unique 5-amino acid insert whose location in the SH3 consensus sequence is the same as that of the inserts found in the SH3 domains of neuronal SRC and of the p85 subunit of phosphatidylinositol 3-kinase.
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PMID:Identification and characterization of SPRK, a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity. 819 46

We studied 36 DNA samples of 18 patients affected with chronic myeloid leukemia (CML) for the presence of mutations in the first exon of the BCR gene was divided into four regions amplified by polymerase chain reaction (PCR). By single strand conformation polymorphism analysis (SSCP) and direct sequencing of amplified fragments, we found different banding profiles in 9 out of 18 patients in the PCR fragment spanning nucleotide 506-826. In one patient, sequence analysis revealed the presence of a point mutation at nucleotide 669 (A-T; Gln-Leu). No difference was found between DNA samples collected during the chronic phase and the blastic transformation. No different mobility shifts of single stranded PCR products were found in the other amplified fragments. The activation of BCR-ABL involves direct interaction between BCR first exon sequences and the tyrosine kinase regulatory domains of ABL. In the first BCR exon, and around the mutated sequences two SH-2-binding sites, are retained. These domains are essential for BCR-ABL-mediated transformation. Our results demonstrate the presence of point mutation in this regulatory region, which may suggest a role for the altered BCR sequence in activation of the BCR-ABL oncogene.
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PMID:Structural organization of BCR-ABL gene in chronic phase and blast transformation in chronic myeloid leukemia patients. 825 17

NCC recognize a conserved target cell antigen (NKTag) expressed on protozoan parasites and on transformed tumour cells. In the present study, synthetic peptides corresponding to N-terminal, C-terminal and internal NKTag(deduced) amino acid sequences were tested for binding and inhibition of NCC lysis of sensitive target cells. A 20-mer peptide equivalent to amino acids (aa) nos. 55-74 specifically inhibited NCC lysis of human EBV transformed target cells (IM-9). Inhibitory effects were nonreversible and concentration dependent, and 30 min pre-incubation produced optimum inhibition. The inhibitory 20-mer peptide was truncated into 17, 14, 10, 9 and 6-mer peptides and tested for inhibition of cytotoxicity. All produced almost complete inhibition except the 6-mer which had no activity. The NKTag sequence required for NCC binding (minimally) consisted of seven amino acids [aa nos 68-74 (ARG-ASN-LEU-THR-PHE-ILE-LEU-)]. The specificity of inhibition and the distribution of target cells expressing NKTag was determined. A 14-mer peptide composed of aa nos 61-74 inhibited lysis of HL-60, IM-9, DAUDI, YAC-1, U937 and NC-37 target cells. Flanking peptides (aa nos 35-54 and 75-94) were negative. Biotinylated aa nos 61-74 bound to NCC effector cells. The recognition requirements for aa sequence versus aa content were determined. Randomization of the aa in the cognate 9-mer obliterated the inhibitory effects. The 17-mer (cognate) synthetic peptide inhibited conjugate formation between NCC and IM-9 targets. These data demonstrate that NCC recognize a conserved antigen determinant on susceptible target cells consisting of a minimum of 7-9 amino acids in the N-terminal region of NKTag.
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PMID:Mapping of the epitope recognized by non-specific cytotoxic cells: determination of the fine specificity using synthetic peptides. 863 15

Malate synthase is a glyoxysome-specific enzyme. The carboxy-terminal tripeptide of the enzyme is Ser-Arg-Leu (SRL), which is known to function as a peroxisomal targeting signal in mammalian cells. To analyze the function of the carboxy-terminal amino acids of pumpkin malate synthase in plant cells, a chimeric gene was constructed that encoded a fusion protein which consisted of beta-glucuronidase and the carboxyl terminus of the enzyme. The fusion protein was expressed and accumulated in transgenic Arabidopsis that had been transformed with the chimeric gene. Immunocytochemical analysis of the transgenic plants revealed that the carboxy-terminal five amino acids of pumpkin malate synthase were sufficient for transport of the fusion protein into glyoxysomes in etiolated cotyledons, into leaf peroxisomes in green cotyledons and in mature leaves, and into unspecialized microbodies in roots, although the fusion protein was no longer transported into microbodies when SRL at the carboxyl terminus was deleted. Transport of proteins into glyoxysomes and leaf peroxisomes was also observed when the carboxy-terminal amino acids of the fusion protein were changed from SRL to SKL, SRM, ARL or PRL. The results suggest that tripeptides with S, A or P at the -3 position, K or R at the -2 position, and L or M at the carboxyl terminal position can function as a targeting signal for three kinds of plant microbody.
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PMID:Transport of chimeric proteins that contain a carboxy-terminal targeting signal into plant microbodies. 877 80

The novel substance P (SP) analogue, [D-Arg1,D-Trp5,7,9,Leu11]SP like [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP inhibited DNA synthesis induced by bombesin, vasopressin, and bradykinin, but did not interfere with the mitogenic response induced by other growth factors or pharmacological agents in Swiss 3T3 cells. [D-Arg1,D-Trp5, 7,9,Leu11]SP reversibly inhibited bombesin-induced DNA synthesis, causing a 6-fold greater rightward shift in the bombesin dose response than [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP at identical concentrations (10 microM). We found that the new, more potent, SP analogue coordinately and reversibly inhibited bombesin-induced Ca2+ mobilization and protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation. The dose-response curves for bombesin-induced Ca2+ mobilization and MAP kinase activation were similarly displaced (51- and 40-fold, respectively) by [D-Arg1, D-Trp5,7,9,Leu11]SP. In addition, [D-Arg1,D-Trp5,7,9,Leu11]SP reversibly inhibited bombesin-induced tyrosine phosphorylation of Mr 110,000-130,000 and 70,000-80,000 bands as well as p125 focal adhesion kinase. [D-Arg1,D-Trp5,7,9,Leu11]SP also reversibly and coordinately inhibited vasopressin-induced Ca2+ mobilization, PKC stimulation, MAP kinase activation, tyrosine phosphorylation, and DNA synthesis in Swiss 3T3 cells. Surprisingly, deletion of the terminal Leu of [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP to yield [D-Arg1, D-Phe5,D-Trp7,9]SP1-10 resulted in a selective loss of inhibitory activity of this analogue against bombesin- but not vasopressin-stimulated DNA synthesis, Ca2+ mobilization, and MAP kinase activation. Collectively, these results suggest that SP analogues act at the receptor level to coordinately and reversibly antagonize bombesin- or vasopressin-induced signal transduction in Swiss 3T3 cells.
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PMID:[D-Arg1,D-Trp5,7,9,Leu11]Substance P coordinately and reversibly inhibits bombesin- and vasopressin-induced signal transduction pathways in Swiss 3T3 cells. 891 Jun 12


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