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)

The conditions were evolved and checked for simultaneous determination of cadmium and lead levels in plant material using the flame technique of ASA. For decomposition of the organic substances in plant material wet mineralization was used with a mixture of nitric acid, perchloric acid and sulpuric acid in volume proportions 6:2:0.25. The levels of cadmium and lead were determined in the organic phase after extraction with n-butyl acetate of the previously produced complexes with NaDDTK. The obtained limits of cadmium and lead detectability were 0.002 and 0.02 mg/kg respectively. The recovery rate of the method ranged from 96 to 98%, while the variability index was from 2.6 to 10.2%. The correctness of the evolved analytical procedure was confirmed by determination of the content of both elements in the NBS-SRM 1571 standard (orchard leaves) and by participation in the international interlaboratory investigation of the Polish standard (dried cabbage leaves).
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PMID:[A method of atomic absorption spectrophotometry (AAS) for analysis of cadmium and lead levels in the plant material]. 210 Nov 73

We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c-Mpl ligand, on human platelets. TPO induced rapid dose-dependent tyrosine phosphorylation of several proteins. We identified Janus tyrosine kinases, Tyk2 and JAK2, and a member of STAT (signal transducers and activators of transcription) family, STAT3, as the tyrosine-phosphorylated proteins in response to TPO. TPO by itself did not cause platelet aggregation and shape change, but augmented ADP-induced aggregation in a dose-dependent manner. Acetylsalicylic acid inhibited the secondary aggregation enhanced by TPO, but not the TPO-induced potentiation of the primary aggregation. TPO modulates platelet activation possibly through protein-tyrosine phosphorylation.
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PMID:Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists-induced aggregation in platelets in vitro. 758 10

The migration of arterial vascular smooth muscle cells (VSMC) is thought to play a central role in atherogenesis and restenosis. The migration of several other cell types, including monocytes, T-lymphocytes and endothelial cells is also involved in the development of the mature atherosclerotic lesion. Several defined growth factors, cytokines and extracellular matrix components which are released at the sites of lesions have been implicated in the regulation of migration of VSMC and other lesion-associated cells. Platelet-derived growth factor BB-homodimer of PDGF (PDGF-BB) is strongly implicated in neo-intima formation in vivo and is the most potent known chemoattractant for VSMC in vitro. Dynamic interactions between cell surface adhesive receptors (integrins) for ECM components, organisation of the actin cytoskeleton and the turnover of focal adhesions are all key processes in cell locomotion and migration. The signal transduction pathways which mediate the chemotactic effects of PDGF-BB and other migration factors on VSMC are unknown, but several classes of cellular components are implicated including components associated with focal adhesions, small GTP-binding proteins of the rho family, and certain substrates of the PDGF beta-receptor. Tyrosine phosphorylation of the novel focal adhesion-associated protein tyrosine kinase, p125 focal adhesion kinase (p125FAK), is regulated by integrins and by several factors which alter actin cytoskeletal organisation. Recent findings suggest that tyrosine phosphorylation of p125FAK and other focal adhesion-associated proteins may be implicated in the chemotactic response of VSMC to PDGF-BB. The migratory response to PDGF-BB may be dependent on both ligand isoform bio-availability and on receptor-isotype expression as well as on down-stream signalling events. Ultimately, cell migration in vivo will be determined by a complex array of diverse extracellular molecules organised in intercellular paracrine/autocrine networks as well as multiple interacting intracellular signal transduction pathways.
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PMID:Signalling mechanisms in the regulation of vascular cell migration. 857 3

The product of the c-myc proto-oncogene has a central role in induction of apoptosis, a physiological form of cell death characterised in vitro by morphological rounding, detachment and nuclear disintegration. Induction of apoptosis by serum withdrawal from c-Myc-transformed chicken embryo fibroblasts (CEF) results in early proteolysis of focal adhesion kinase (ppl25FAK), a tyrosine kinase implicated in the conversion of integrin signals into their biological responses. Proteolysis of pp125 FAK occurs in adherent cells prior to commitment to death, suggesting that it contributes to c-Myc-induced apoptosis, rather than being a consequence of it. Furthermore, c-Myc-induced detachment, cell death and cleavage of pp125FAK are coordinately suppressed by treating with insulin or plating on the extracellular matrix components collagen and fibronectin. In addition, proteolysis of pp125FAK is suppressed by a beta1-specific integrin antibody, which promotes cell survival in the face of the oncoprotein-induced signal for apoptosis. These results provide compelling evidence that the c-Myc-induced cell death programme in CEF requires disruption of the integrin signalling pathways which normally function when cells are spread on ECM, and that maintaining cellular pp125FAK, which couples integrins to their downstream effectors, is closely linked to cell survival.
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PMID:Targeted proteolysis of the focal adhesion kinase pp125 FAK during c-MYC-induced apoptosis is suppressed by integrin signalling. 870 May 28

Previous studies have shown that Schwann cells (SCs) differentiate into myelin-forming or ensheathing cells only under conditions which allow the deposition of basal lamina and extracellular collagen [Bunge (1993) Peripheral Neuropathy, pp. 299-316]. SC adhesion to basal lamina is mediated by beta1 integrins and function blocking antibodies to beta1 integrins inhibit myelination [Fernandez-Valle et al. (1993) Development 119:867-880]. Recently, focal adhesion kinase (FAK), a cytoplasmic non-receptor tyrosine kinase, was found to mediate beta1 integrin-dependent signalling in a variety of cultured cell types adhering to ECM components such as fibronectin [reviewed in Schwartz et al. (1995) Ann. Rev. Cell Biol. 11:549-599; Ilic et al. (1997) J. Cell Sci. 110:401-407]. In the present study, we have determined more precisely the respective time courses of ECM deposition and myelination. In addition, we have studied by immunocytochemistry, immuno-gold labelling, and electron microscopy the expression and subcellular localization of FAK in nondifferentiating SCs and in SCs differentiating into myelinating cells. We show that the development of basal lamina and extracellular collagen fibrils precedes by 3 days the appearance of the first myelin sheaths. FAK was detected by immunocytochemistry or immuno-gold labelling only in SCs differentiating in the presence of ascorbic acid. Localization of FAK to the abaxonal plasma membrane was dependent upon ECM deposition. Cytochalasin D did not prevent or disrupt localization of FAK to the plasma membrane. These data support the possibility that FAK acts as an intermediate in the pathway by which basal lamina regulates SC differentiation.
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PMID:Localization of focal adhesion kinase in differentiating Schwann cell/neuron cultures. 967 24

The dramatic increase in uterine growth during late pregnancy and the generation of labor contractions require dynamic remodeling of myometrial smooth muscle-ECM interactions. In many tissues, such interactions are provided by focal adhesions; however, there are no data as to the expression of focal adhesion proteins or of focal adhesion signaling in the myometrium. In this study, we show that tyrosine phosphorylation of myometrial FAK (FAK-P-Tyr) and of its downstream substrate, paxillin, exhibited a >10-fold increase during late pregnancy (days 15-22 of pregnancy) with each exhibiting a dramatic fall in P-Tyr on day 23 in association with the onset of labor. These changes in FAK-P-Tyr were paralleled by changes in FAK enzyme activity. Activated ERK1 and ERK2 expression remained relatively unchanged from day 15 to day 23, but decreased markedly 1 day post partum. Treatment of late pregnant rats with progesterone prevented the fall in FAK-P-Tyr/enzyme activity on day 23, and also blocked the onset of labor. These data suggest that progesterone (which decreases at term) modulates myometrial FAK activity/focal adhesion signaling and that these changes may underlie the tremendous remodeling that must occur in order for this muscle to develop optimal contractile activity during labor.
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PMID:Focal adhesion signaling in the rat myometrium is abruptly terminated with the onset of labor. 1061 48

The signaling pathways critical for cell survival are mediated in part by the composition and integrity of the extracellular matrix and the action of its components on specific cell adhesion receptors. Withdrawal of anchorage-dependent epithelial cells from their association with ECM results in apoptotic cell death. Consistently, the matrix metalloproteinases (MMPs) or their inhibitors (TIMPs) have been suggested to regulate apoptosis. In this report, we investigated whether bcl-2 inhibition of apoptosis involves regulation of TIMP expression. We have found that bcl-2 overexpression induces TIMP-1 expression in breast epithelial cell lines (MCF10A, MCF10AneoT.TG3B, and MCF-7), whereas it has no effect on TIMP-2 expression. We demonstrated that TIMP-1 inhibits cell death induced by hydrogen peroxide, Adriamycin, or X-ray irradiation. In addition, TIMP-1 overexpression inhibits apoptosis after the loss of cell adhesion (anoikis) in MCF10A cells, suggesting that the antiapoptotic activity of TIMP-1 does not depend on its ability to stabilize cell-matrix interactions. We also showed that TIMP-1 overexpression is associated with constitutive activation of focal adhesion kinase, a signaling molecule known to be critical for the cell survival pathway.
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PMID:Tissue inhibitor of metalloproteinase-1 inhibits apoptosis of human breast epithelial cells. 1062 22

Pulmonary enzyme heme oxygenase, which catalyses carbon monoxide production, may be responsible for arteriovenous carboxyhemoglobin (COHb) differences measured in humans. Unspecific inflammatory stimuli have been shown to induce pulmonary heme oxygenase possibly leading to increased pulmonary carbon monoxide production and elevated arterial COHb. Arteriovenous COHb gradients may therefore be a measurable parameter of lung injury severity. To exclude a technical artefact, we repeated measurements of central venous COHb and arterial COHb in healthy humans (ASA I-II) undergoing elective surgery with the ABL 625 and the updated version, ABL 725 (Radiometer, Copenhagen). In addition to the standard calibration, an especially accurate adjustment of the spectrophotometer wavelengths (SAT100) was performed. This adjustment eliminates the FCOHb dependency on the oxygen saturation. No significant differences were detectable between central venous and arterial COHb concentrations with either blood gas analyzer. The difference between central venous COHb and arterial COHb was 0.09 with the ABL 625 and -0.03 with the ABL 725. Therefore, we conclude that previously reported arteriovenous COHb differences are artifactual and may be eliminated by SAT 100 adjustment, as is possible with the ABL 725.
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PMID:Arteriovenous carboxyhemoglobin gradient is a technical artifact that is eliminated by special calibration (SAT 100). 1109 56

Prolidase [E.C. 3.4.13.9] plays an important role in the recycling of proline for collagen synthesis and cell growth and this enzyme activity determines the rate of collagen turnover. It has been previously suggested that prolidase activity is regulated through signal mediated by the interaction of ECM proteins, with b1 integrin receptor and that this interaction is disturbed in MCF-7 cells. The potential candidates for mediating signal transduction are the nonreceptor tyrosine kinase p125FAK and two mitogen-activated protein (MAP) kinases, ERK-1 and ERK-2, which are activated upon attachment of cells to ECM. We found that serum starvation of MCF-7 cells for 24 hours contributed to a significant decrease (by about 30%) in prolidase activity and collagen biosynthesis. These phenomena were accompanied by suppression of MAP kinases expression without any effect on the expression of FAK. The data suggest that prolidase activity and collagen biosynthesis respond to signal mediated by MAP kinases, independently of FAK expression in MCF-7 cells.
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PMID:FAK-independent regulation of prolidase activity and collagen biosynthesis in MCF-7 cells. 1182 Jun 13

We have previously shown that microtubule disruption results in an increase in cell adhesion to ECM proteins. In this work we show that this enhanced cell attachment was completely abolished by specific inhibitors of tyrosine-kinases, PI3-K and PKCs. Microtubule depolymerisation was associated with an important increased in tyrosine phosphorylation of FAK and paxilline, as well as with subcellular localisation of PKCgamma, delta and epsilon. We also observed significant alterations in actin cytoskeleton leading to reduced cell spreading. Thus, microtubule depolymerisation appears to activate various intracellular kinases that lead to actin cytoskeletal changes and to an increase of integrin-dependent adhesion. Whether this enhanced attachment is due to intracellular events resulting in changes in integrin affinity or avidity remains to be determined.
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PMID:[Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption]. 1188 61


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