Nanopublications LDF server

Matches in Nanopublications for { ?s <http://www.w3.org/ns/prov#value> ?o ?g. }

• _7 value "Migration of all leukocytes depends mainly on β2 integrins (Mac-1 and LFA-1) and on ICAM-1, their ligand on endothelial cells." provenance.
• _4 value "Specific increased expression of glycolytic enzymes, glucose tranporter GLUT-1, VEGF, tyrosine hydroxylase, transferrin, and erythropoietin is observed, all proteins involved in the adaptative response of cells to hypoxia." provenance.
• _4 value "Specific increased expression of glycolytic enzymes, glucose tranporter GLUT-1, VEGF, tyrosine hydroxylase, transferrin, and erythropoietin is observed, all proteins involved in the adaptative response of cells to hypoxia." provenance.
• _4 value "Numerous molecules stimulate endothelial proliferation and migration, including VEGF, Ang1, and bFGF." provenance.
• _4 value "Numerous molecules stimulate endothelial proliferation and migration, including VEGF, Ang1, and bFGF." provenance.
• _4 value "Numerous molecules stimulate endothelial proliferation and migration, including VEGF, Ang1, and bFGF." provenance.
• _4 value "Numerous molecules stimulate endothelial proliferation and migration, including VEGF, Ang1, and bFGF." provenance.
• _3 value "Oxidation and nitration of macromolecules, such as proteins, DNA and lipids, are prominent in atherosclerotic arteries." provenance.
• _3 value "Aging, one of the major predictors for atherosclerotic lesion formation, increases the sensitivity of endothelial cells to apoptosis induced by in vitro and in vivo stimuli [35–37]." provenance.
• _5 value "Shear stress enhances expression of the gene encoding the endothelial nitric oxide synthase (eNOS) and further stimulates its enzymatic activity, leading to physiologic low concentrations of nitric oxide (NO) within endothelial cells [44–46]. This continuous generation of NO prevents the apoptosis of endothelial cells, thereby protecting the endothelial monolayer from injury [47,48]." provenance.
• _3 value "For instance, during 7-ketocholesterol-induced apoptosis of U937 cells, the cellular antioxidant content falls rapidly [64], but administration of two potent antioxidants, the aminothiols glutathione and N-acetylcysteine, can protect themonocytic cells from 7-ketocholesterol-induced apoptotic cell death [64]." provenance.
• _5 value "In addition, another oxygen-radical scavenger enzyme, catalase, can prevent VSMC apoptosis triggered by hydrogen peroxide [27,65]." provenance.
• _4 value "The proto-oncogene c-myc can promote cell death (probably mediated through p53) or cell proliferation, depending on its expression level. It functions as a nuclear phosphoprotein with particular properties of a transcription factor [68,69]. In serum deprived cultures, cells overexpressing c-myc readily undergo apoptosis. In addition, deregulation of c-myc causes apoptosis of VSMCs deprived of growth factors or treated with cytokines such as interferon-g [70]." provenance.
• _4 value "The proto-oncogene c-myc can promote cell death (probably mediated through p53) or cell proliferation, depending on its expression level. It functions as a nuclear phosphoprotein with particular properties of a transcription factor [68,69]. In serum deprived cultures, cells overexpressing c-myc readily undergo apoptosis. In addition, deregulation of c-myc causes apoptosis of VSMCs deprived of growth factors or treated with cytokines such as interferon-g [70]." provenance.
• _9 value "Tissue factor (TF) is a 47 kDa transmembrane glycoprotein that initiates blood coagulation by binding coagulation factor VII and its activated form (factor VIIa), to produce a high-affinity complex [72] that proteolytically activates factors IX and X, leading to thrombin generation." provenance.
• _3 value "TF works at the surface of cell membranes, and its activity is highly dependent on the presence of phosphatidylserine (PS), an anionic phospholipid that is redistributed on the cell surface during apoptotic death and confers a potent pro-coagulant activity to the apoptotic cell [74]." provenance.
• _3 value "TF works at the surface of cell membranes, and its activity is highly dependent on the presence of phosphatidylserine (PS), an anionic phospholipid that is redistributed on the cell surface during apoptotic death and confers a potent pro-coagulant activity to the apoptotic cell [74]." provenance.
• _4 value "TIMP-3 can be anti-angiogenic by direct binding to vascular endothelial growth factor (VEGF) receptor 2 in a matrix-metalloproteinase- independent manner [94]." provenance.
• _5 value "We next examined the Akt T-loop Thr308 phosphorylation in wild-type and SIN1−/− cells. We found that although Ser473 phosphorylation was completely abolished in the SIN1−/− cells, Thr308 phosphorylation of Akt was not blocked (Figure 3A)." provenance.
• _6 value "We also examined phosphorylation of TSC2, another Akt target (Manning et al., 2002), at the Akt target sites Ser939 and Thr1462 and found no significant difference between wild-type and SIN1−/− cells upon serum and insulin stimulation (Figure 3C)." provenance.
• _5 value "To identify a function that could be linked specifically to Akt-Ser473 phosphorylation, we further examined known Akt substrates that may have defective phosphorylation in SIN1−/− cells. We found that phosphorylation of FoxO1/3a (also called FKHR/FKHRL1) (Greer and Brunet, 2005), was affected in SIN1−/− cells. In particular, phosphorylation of FoxO1/3a at Thr24/Thr32 was significantly decreased in the absence of SIN1 under normal growing and restimulated conditions (Figure 4A)." provenance.
• _5 value "To identify a function that could be linked specifically to Akt-Ser473 phosphorylation, we further examined known Akt substrates that may have defective phosphorylation in SIN1−/− cells. We found that phosphorylation of FoxO1/3a (also called FKHR/FKHRL1) (Greer and Brunet, 2005), was affected in SIN1−/− cells. In particular, phosphorylation of FoxO1/3a at Thr24/Thr32 was significantly decreased in the absence of SIN1 under normal growing and restimulated conditions (Figure 4A)." provenance.
• _6 value "To identify a function that could be linked specifically to Akt-Ser473 phosphorylation, we further examined known Akt substrates that may have defective phosphorylation in SIN1−/− cells. We found that phosphorylation of FoxO1/3a (also called FKHR/FKHRL1) (Greer and Brunet, 2005), was affected in SIN1−/− cells. In particular, phosphorylation of FoxO1/3a at Thr24/Thr32 was significantly decreased in the absence of SIN1 under normal growing and restimulated conditions (Figure 4A)." provenance.
• _4 value "In etoposide-treated cells, there was a 2-fold increase in the number of cells that underwent apoptosis after 48 hr in SIN1 knockouts (Figure 4D). Thus, we find that the SIN1−/− cells were more sensitive to stress-induced apoptosis, suggesting that Akt-Ser473 phosphorylation plays an important role in cell survival (Figures 4C and 4D)." provenance.
• _5 value "Likewise, phosphorylation of another translational regulator, 4E-BP1, at the mTOR target site Thr37/46 (Gingras et al., 1999), was also not impaired in SIN1−/− cells (Figure 5A)." provenance.
• _6 value "Likewise, phosphorylation of another translational regulator, 4E-BP1, at the mTOR target site Thr37/46 (Gingras et al., 1999), was also not impaired in SIN1��/− cells (Figure 5A)." provenance.
• _5 value "Akt Ser473 was strongly induced in wild-type cells by different growth factors such as the platelet-derived growth factor, epidermal growth factor, and insulin, even in the absence of amino acids and glucose (Figure 5B). In SIN1−/− cells, Akt-Ser473 phosphorylation was not induced by any type of stimulus." provenance.
• _5 value "As shown in Figures 5E and 5F, SIN1 was able to associate with Akt under normal growth, starvation, or restimulated conditions. Although SIN1 and Akt interacted under starved condition, the SIN1 bound Akt was not phosphorylated on Ser473 (Figure 5E)." provenance.
• _4 value "For example, the inactivation of VHL has been demonstrated in 70–80% of all sporadic clear cell RCC, the major form of RCC, which accounts for ~2% of all cancer deaths worldwide [8]." provenance.
• _8 value "The best-established function of pVHL to date has been as a substrate recognition component of an E3 ubiquitinprotein ligase complex, comprising pVHL, Elongin C, Elongin B, Cullin 2 and the RING finger protein, Rbx1, and this is referred to as the VCB–Cul2 complex [17]." provenance.
• _7 value "In this setting, pVHL targets the α-subunits of hypoxiainducible factor (HIF) for ubiquitin-mediated proteolysis under normal oxygen conditions [18]." provenance.
• _4 value "The VHL-mediated proteolytic degradation of HIF suppresses a transcription programme that is normally engaged by HIF as part of the adaptive response of the cell to hypoxia, such as the activation of vascular endothelial growth factor (VEGF), which is a potent angiogenic factor that is involved in the formation and differentiation of blood vessels." provenance.
• _6 value "Transcriptional control is also maintained by a specific acetylation (Ac) event at lysine 532 and an additional asparagine hydroxylation (OH) event at position 863, both of which act as negative regulators of the transcriptional activity of HIF." provenance.
• _5 value "Nevertheless, the restored ability of pVHL-positive transfectants to assemble extracellular fibronectin was mediated by b1 integrins, implying that pVHL controls ECM assembly, at least in part, through integrin signalling [46]. A recent development has demonstrated that an ubiquitin-like molecule, NEDD8, covalently modifies pVHL and that a neddylation- defective pVHL mutant, despite retaining its ability to degrade HIF, fails to promote the assembly of a fibronectin matrix [47]." provenance.
• _6 value "The regulation of insulin growth factor (IGF)-I-mediated cell invasion of RCC cells appears to be dependent upon PKCd inhibition by pVHL. This inhibition is mediated through a protein–protein interaction involving a domain of pVHL that shows similarity to protein kinase inhibitor (PKI), a natural inhibitor of cAMP-dependent protein kinase (PKA) [48]" provenance.
• _5 value "The considerable attention paid to targeting Ras as a therapeutic strategy is based on the high incidence of activating ras mutations in human malignancies, including approximately 22% of non–small-cell lung, 50% of colorectal, and 90% of pancreatic cancers. 53,60,61" provenance.
• _5 value "Localization of GTP-bound Ras to the inner surface of the cell membrane activates several downstream effectors, most notably the serine/threonine kinase Raf, which is the first signaling element in the MAPK pathway. 2,67,68 As shown in Figure 1, other downstream effectors of Ras include the PI3K cell survival pathway, the small GTP-binding proteins Rac and Rho, and the stress-activated protein kinase pathway (also referred to as the c-jun N-terminal kinase [JNK] pathway). 69-71 In addition, in response to cellular stress and cytokine stimulation mediated through Ras, the dual-specificity p38MAPK kinases (MKK3 and MKK6) and the JNK kinases (MKK4 and MKK7) phosphorylate p38MAPK and JNK, respectively. 72-76" provenance.
• _5 value "Localization of GTP-bound Ras to the inner surface of the cell membrane activates several downstream effectors, most notably the serine/threonine kinase Raf, which is the first signaling element in the MAPK pathway. 2,67,68 As shown in Figure 1, other downstream effectors of Ras include the PI3K cell survival pathway, the small GTP-binding proteins Rac and Rho, and the stress-activated protein kinase pathway (also referred to as the c-jun N-terminal kinase [JNK] pathway). 69-71 In addition, in response to cellular stress and cytokine stimulation mediated through Ras, the dual-specificity p38MAPK kinases (MKK3 and MKK6) and the JNK kinases (MKK4 and MKK7) phosphorylate p38MAPK and JNK, respectively. 72-76" provenance.
• _7 value "GTP-bound Ras interacts directly with Raf and mobilizes the inactive protein from the cytoplasm (Figs 1 and 2). Once the Ras-Raf complex is translocated to the cell membrane, Ras activates the serine/threonine kinase function of Raf through an association between its Ras-binding domain (RBD) in the amino-terminal regulatory region and Ras-GTP." provenance.
• _7 value "Raf is also activated by Ras-independent activators, including the soluble non-RTK Src and Janus kinase 1, which are involved in cytokine signaling.86 Other Ras-independent activators of Raf include interferon beta, protein kinase C (PKC) alpha, antiapoptotic proteins (eg, Bcl-2), scaffolding proteins (eg, ceramide-activated protein kinase), ultraviolet light, ionizing radiation, retinoids, erythropoietin, and dimerization between Raf isoforms 86-94 (Fig 3)." provenance.
• _5 value "Furthermore, the kinase activity of Raf is inhibited by its interactions with cholesterol-rich lipid rafts in the cell membrane and phosphorylation by protein kinases A (PKA) and B (PKB/Akt), as shown in Figure 2.95-98" provenance.
• _7 value "Additional support for the diverse functionality of Raf family members is provided by the disparate responses of B-Raf and C-Raf to identical stimuli, as well as the distinct messages that each isoform relays downstream to Rap1, which is a small GTPase that functions as both an activator and repressor of Raf.115 Rap1-mediated stimulation of B-Raf by cyclic adenosine monophosphate (cAMP) phosphorylates ERK, whereas stimulation of C-Raf inhibits ERK phosphorylation.115" provenance.
• _7 value "With regard to differences in signaling between the Raf isoforms, A-Raf is a weaker activator of MEK than B-Raf or C-Raf. Furthermore, A-Raf can activate MEK1 only, whereas C-Raf activates both MEK1 and MEK2.123-125" provenance.
• _6 value "C-Raf exists in the cytoplasm as a 300- to 500-kd protein complex. The complex consists of C-Raf, heat shock protein 90 (Hsp90), and the dimeric protein cofactor 14-3-3. 14-3-3 binds to two specific phosphoserine residues of C-Raf, which masks its kinase domain and inactivates the protein. The binding of Ras to C-Raf displaces the 14-3-3 dimer, rendering C-Raf accessible to dephosphorylation by protein phosphatase 2A.126" provenance.
• _7 value "The effector domain of GTP-bound Ras binds to C-Raf through the RBD and CRD in the CR1. Although binding to both sites is required for Raf activation, the most critical interaction is between Ras-GTP and the RBD.127 All Ras isoforms are capable of interacting with Raf, but K-Ras is the most potent activator, whereas N-Ras is much more efficient than H-Ras.128 The interaction between Ras and C-Raf alone is insufficient to activate C-Raf, but it serves to translocate C-Raf to the cell membrane where it can be activated." provenance.
• _8 value "The activation of B-Raf by Ras has been less well studied; however, the interacting amino acids in the Ras-Raf interface are identical for B-Raf and C-Raf.129,130 The association of Ras with B-Raf also translocates B-Raf to the cell membrane where it is activated.124 Interestingly, a membrane-free complex of B-Raf and 14-3-3 can be activated in vitro by recombinant Ras. This is in stark contrast to A-Raf and C-Raf, which must undergo a series of phosphorylation reactions on serine and tyrosine residues in the cell membrane and cannot be activated by Ras alone.124,130 Of the Raf isoforms, B-Raf is activated first, and on stimulation by Ras, it heterodimerizes with C-Raf, the significance of which is not known.94" provenance.
• _7 value "Both B-Raf and C-Raf can bind to other small GTPases, most notably Rap1.115,131,132 The effector domains of Rap1 and Ras are nearly identical, but activation of these proteins produces vastly different downstream effects. Furthermore, Rap1 mediates distinct effects after binding to various Raf isoforms. The B-Raf–Rap1 complex activates B-Raf, whereas the C-Raf–Rap1 interaction does not activate C-Raf and, in fact, may be inhibitory.115,132,133 This occurs because Rap1 binds to the CRD of C-Raf with higher affinity than Ras and excludes Ras from binding." provenance.
• _7 value "The Rho family of small GTPases, consisting of Rho, Rac, and cyclin-dependent kinase (Cdc) 42, regulate cytoskeletal organization during the cell cycle and also mediate Ras-induced activation of Raf, especially C-Raf.134-136 These GTPases do not directly bind to Raf but, instead, signal by activating downstream kinases. Rho signals by activating the serine/threonine protein kinases N1 and N2 and Rho-associated kinase 1, whereas Rac and Cdc42 signal through p21-activated kinase (PAK).134-136" provenance.
• _7 value "The Rho family of small GTPases, consisting of Rho, Rac, and cyclin-dependent kinase (Cdc) 42, regulate cytoskeletal organization during the cell cycle and also mediate Ras-induced activation of Raf, especially C-Raf.134-136 These GTPases do not directly bind to Raf but, instead, signal by activating downstream kinases. Rho signals by activating the serine/threonine protein kinases N1 and N2 and Rho-associated kinase 1, whereas Rac and Cdc42 signal through p21-activated kinase (PAK).134-136" provenance.
• _6 value "Phosphorylation. Raf is principally activated by phosphorylation of specific amino acid residues as shown for each isoform in Figure 4. From an evolutionary standpoint, the Raf activation sites are highly conserved from yeast to humans. Several amino acids in Raf, particularly serine (S) 259 and S621, which bind 14-3-3 and maintain C-Raf in a closed auto-inhibited conformation, are phosphorylated in the basal state.137 On stimulation, Ras-GTP displaces 14-3-3 from S259, and C-Raf is translocated to the cell membrane, where it can be dephosphorylated at S259 by protein phosphatase 2A or other phosphatases.126 S259 also represents the site of inhibitory phosphorylation by PKB/Akt, PKA, and serum glucocorticoid-inducible kinase.121,138,139 Phosphorylation at S621 seems to have greater significance because mutations at this site inactivate Raf's kinase activity. Hence, a balance of phosphorylation and dephosphorylation is required to prime Raf in the basal state before stimulation by Ras or mitogens.137" provenance.
• _6 value "Raf is also phosphorylated at other serine and threonine residues, the most important of which are S338 and tyrosine (Y) 341, which are situated adjacent to the C-Raf kinase domain.140 Phosphorylation of these residues relieves the inhibitory effects of the regulatory domain on the kinase domain.141 S338, which is the evolutionarily conserved PAK phosphorylation site that resides on the amino-terminal side of the kinase domain, is critical for Raf activation.134-136,140,142 This site is also phosphorylated in response to stimulation by growth factors, integrins, Ras, PAK1, and PAK3.78,136,143" provenance.
• _6 value "Raf is also phosphorylated at other serine and threonine residues, the most important of which are S338 and tyrosine (Y) 341, which are situated adjacent to the C-Raf kinase domain.140 Phosphorylation of these residues relieves the inhibitory effects of the regulatory domain on the kinase domain.141 S338, which is the evolutionarily conserved PAK phosphorylation site that resides on the amino-terminal side of the kinase domain, is critical for Raf activation.134-136,140,142 This site is also phosphorylated in response to stimulation by growth factors, integrins, Ras, PAK1, and PAK3.78,136,143" provenance.
• _6 value "Raf is also phosphorylated at other serine and threonine residues, the most important of which are S338 and tyrosine (Y) 341, which are situated adjacent to the C-Raf kinase domain.140 Phosphorylation of these residues relieves the inhibitory effects of the regulatory domain on the kinase domain.141 S338, which is the evolutionarily conserved PAK phosphorylation site that resides on the amino-terminal side of the kinase domain, is critical for Raf activation.134-136,140,142 This site is also phosphorylated in response to stimulation by growth factors, integrins, Ras, PAK1, and PAK3.78,136,143" provenance.
• _4 value "Raf is also phosphorylated at other serine and threonine residues, the most important of which are S338 and tyrosine (Y) 341, which are situated adjacent to the C-Raf kinase domain.140 Phosphorylation of these residues relieves the inhibitory effects of the regulatory domain on the kinase domain.141 S338, which is the evolutionarily conserved PAK phosphorylation site that resides on the amino-terminal side of the kinase domain, is critical for Raf activation.134-136,140,142 This site is also phosphorylated in response to stimulation by growth factors, integrins, Ras, PAK1, and PAK3.78,136,143" provenance.
• _5 value "As shown in Figure 2, C-Raf interacts with a diverse array of scaffolding proteins (kinase suppressor of Ras and MEK partner-1), adaptor proteins (Bcl-2–associated athanogene-1), chaperone proteins (Hsp90 and Hsp70), substrates (retinoblastoma protein [Rb]), lipids (phosphatidic acid, cholesterol-rich caveolae, and cytosolic lipid rafts), and cellular constituents, many of which, in turn, modulate its kinase activity.95" provenance.
• _7 value "The Raf isoforms are the best characterized MEK1 and MEK2 activators, and all Raf isoforms activate MEK1, whereas only B-Raf and C-Raf activate MEK2. MEK1 and MEK2 contain a proline-rich sequence that enables recognition and activation by Raf.125,146-153." provenance.
• _7 value "the dual-specificity p38MAPK kinases (MKK3 and MKK6) and JNK kinases (MKK4 and MKK7) phosphorylate p38MAPK and JNK, respectively.72-76" provenance.
• _6 value "Although both A-Raf and C-Raf are capable of activating other signaling elements independent of MAPK pathway activation, such as nuclear factor-kappa B (NF-κB), Rb, and Bcl-2, MEK1 and MEK2 are the only known substrates for B-Raf.154-157" provenance.
• _6 value "Cell survival signaling is also regulated by C-Raf, which induces phosphorylation of Iκ B in the NF-κB–Iκ B complex. This action releases activated NF-κB, which is then translocated to the nucleus where it mediates transcription of antiapoptotic factors.155,166" provenance.
• _6 value "Other antiapoptotic effects of C-Raf are mediated by a mitochondrial pool of the protein, which, on stimulation, localizes to the mitochondrial membrane where the protein interacts with and phosphorylates Bcl-2, Bcl-2–associated athanogene, and other pro-apoptotic regulators, abrogating their pro-apoptotic effects.157,167 The antiapoptotic effects of C-Raf are also mediated through the ankyrin-repeat protein Tvl-1 and apoptosis signal-regulated kinase-1.166,168,169" provenance.
• _8 value "Other antiapoptotic effects of C-Raf are mediated by a mitochondrial pool of the protein, which, on stimulation, localizes to the mitochondrial membrane where the protein interacts with and phosphorylates Bcl-2, Bcl-2–associated athanogene, and other pro-apoptotic regulators, abrogating their pro-apoptotic effects.157,167 The antiapoptotic effects of C-Raf are also mediated through the ankyrin-repeat protein Tvl-1 and apoptosis signal-regulated kinase-1.166,168,169" provenance.
• _5 value "Somatic B-raf mutations were demonstrated in 60% to 70% of malignant melanomas and in moderate to high rates in carcinomas of the colon, ovary, and thyroid (papillary), implicating activating oncogenic B-raf mutations as critical promoters of these malignancies.9,14-17" provenance.
• _6 value "V599EB-Raf possesses the hallmarks of a conventional oncogene because the kinase activity of its encoded protein is greatly elevated; it constitutively stimulates ERK in vivo in the absence of Ras activation; and it transforms NIH3T3 cells.144" provenance.
• _6 value "Long PDE4 isoforms from all four subfamilies can be activated through PKA phosphorylation [50,54–57] of a single serine residue[50,56,58–61] found at the extreme N-terminal end of UCR1, within the PKA consensus, RRESF." provenance.
• _5 value "cAMP is of pivotal importance in determining many aspects of cellular function [1,2]. It is generated at the cytosol surface of the plasma membrane through the action of adenylate cyclases, of which there is a large family. Increased levels of cAMP are translated into cellular responses through the action of cAMP-dependent protein kinase (PKA)" provenance.
• _6 value "The third subdomain of the catalytic unit of all PDE4 subfamilies, but not that of PDE4A, contains a single, ERK consensus motif (Pro-Xaa-Ser-Pro). The serine residue in this site can be phosphorylated, both in vitro and in vivo , by ERK [49,70,71]." provenance.
• _7 value "ERK phosphorylation of PDE4 long isoforms leads to inhibition under conditions where the serine target is the sole residue phosphorylated [49,70,71]." provenance.
• _7 value "Whether a similar mechanism underpins the ability of interleukin 3 (IL-3) and IL-4 to increase PDE4 activity in myeloid cells through an ERK-mediated process [75], or because ERK-activated short forms predominate in such cells (see above), remains to be seen." provenance.
• _5 value "PA causes a marked (0.7-3-fold) activation of various long PDE4 isoforms, but fails to affect short and super-short isoforms [87,91]. Similar activation was seen with the acidic phospholipid phosphatidylserine (PS), but not with neutral phospholipids." provenance.
• _5 value "PA causes a marked (0.7-3-fold) activation of various long PDE4 isoforms, but fails to affect short and super-short isoforms [87,91]. Similar activation was seen with the acidic phospholipid phosphatidylserine (PS), but not with neutral phospholipids." provenance.
• _3 value "Mitochondrial dysfunction is a major mechanism whereby drugs can induce liver injury and other serious side effects such as lactic acidosis and rhabdomyolysis in some patients." provenance.
• _3 value "drugs can induce microvesicular steatosis, a potentially severe lesion that can be associated with profound hypoglycaemia and encephalopathy" provenance.
• _4 value "When energy is needed (i.e. when ATP levels are low), these protons re-enter the matrix through ATP synthase (also referred to as complex V), thus liberating energy that is used to phosphorylate ADP into ATP." provenance.
• _5 value "Cytochrome c release induces caspase activation and cell death via apoptosis or necrosis." provenance.
• _5 value "Cytochrome c release induces caspase activation and cell death via apoptosis or necrosis." provenance.
• _3 value "a key feature of the mitochondrial genome is its high sensitivity to oxidative damage, because of its proximity to the inner membrane (the main cellular source of ROS)" provenance.
• _6 value "the released cytochrome c binds in the cytosol to Apaf-1 in an ATP-dependent manner to activate caspase-9." provenance.
• _3 value "In contrast, when MPT occurs in most mitochondria in a single cell, ATP generation is compromised because of the collapse of the Δψm, and the resulting ATP depletion triggers cell necrosis [2,24]." provenance.
• _3 value "Mitochondrial permeability transition pore opening, which is calcium-dependent, can be triggered by a variety of endogenous compounds such as iron, ROS, nitric oxide, free fatty acids (and acyl-CoA derivatives), ceramide and bile salts [25,26]." provenance.
• _3 value "Mitochondrial permeability transition pore opening, which is calcium-dependent, can be triggered by a variety of endogenous compounds such as iron, ROS, nitric oxide, free fatty acids (and acyl-CoA derivatives), ceramide and bile salts [25,26]." provenance.
• _4 value "MPT can also be triggered by extracellular cytokines such as tumour necrosis factor-a (TNF-α) and Fas ligand (Fas-L) acting through their plasma membrane receptors [27,28]." provenance.
• _5 value "We show that protein kinase C (PKC) alpha is translocated to the plasma membrane and activated by adhesion of MM cells to fibronectin and VEGF. We identify beta(1) integrin modulating VEGF-triggered MM cell migration on fibronectin. We show that transient enhancement of MM cell adhesion to fibronectin triggered by VEGF is dependent on the activity of both PKC and beta(1) integrin. Moreover, we demonstrate that PKC alpha is constitutively associated with beta(1) integrin." provenance.
• _8 value "We show that protein kinase C (PKC) alpha is translocated to the plasma membrane and activated by adhesion of MM cells to fibronectin and VEGF. We identify beta(1) integrin modulating VEGF-triggered MM cell migration on fibronectin. We show that transient enhancement of MM cell adhesion to fibronectin triggered by VEGF is dependent on the activity of both PKC and beta(1) integrin. Moreover, we demonstrate that PKC alpha is constitutively associated with beta(1) integrin." provenance.
• _6 value "We show that protein kinase C (PKC) alpha is translocated to the plasma membrane and activated by adhesion of MM cells to fibronectin and VEGF. We identify beta(1) integrin modulating VEGF-triggered MM cell migration on fibronectin. We show that transient enhancement of MM cell adhesion to fibronectin triggered by VEGF is dependent on the activity of both PKC and beta(1) integrin. Moreover, we demonstrate that PKC alpha is constitutively associated with beta(1) integrin." provenance.
• _7 value "These data are consistent with PKC alpha-dependent exocytosis of activated beta(1) integrin to the plasma membrane, where its increased surface expression mediates binding to fibronectin; conversely, catalytically active PKC alpha-driven internalization of beta(1) integrin results in MM cell de-adhesion." provenance.
• _5 value "We show that the regulatory subunit of phosphatidylinositol (PI) 3-kinase (p85) is constitutively associated with FMS-like tyrosine kinase-1 (Flt-1). VEGF stimulates activation of PI 3-kinase, and both MM cell adhesion and migration are PI 3-kinase-dependent. Moreover, both VEGF-induced PI 3-kinase activation and beta(1) integrin-mediated binding to fibronectin are required for the recruitment and activation of PKC alpha." provenance.
• _8 value "After VEGF stimulation of cells seeded on fibronectin, PKCα translocated into the membrane fraction after 30 min (Fig. 2a), whereas no significant changes in distribution of PKC isoforms as PKCγ, PKCε, and PKCξ were observed." provenance.
• _8 value "The activation of PKCα after VEGF treatment of cells attached to fibronectin was further supported by a 2-fold increase in PKCα-IP kinase activity;" provenance.
• _7 value "As shown in Fig. 3,d–e, incubation with the PKC inhibitor BIM I (as well as with the β1-neutralizing mAb) blocked dose-dependent VEGF-induced cell adhesion to fibronectin. This involvement of PKC in MM cell adhesion to fibronectin was further confirmed by a dose-dependent increment of adhesion triggered by PMA stimulation (Fig. 3d) similar to that induced by VEGF. Taken together, our results show that VEGF transiently enhances MM cell adhesion to fibronectin, dependent on both PKC and β1 integrin activity." provenance.
• _8 value "(a) Co-immunoprecipitation of CADTK and β1-integrin with PKCα. (b) constitutive association of Flt-1 and CADTK. (c) activation of CADTK upon treatment with PMA (300nM), 20 min. (d) Additional increase of CADTK-phosphorylation in the presence of VEGF (100ng/mL). (e) Dependency of VEGF-induced CADTK activation on PKC and β1-integrin. β1, β1-integrin; pY, phosphotyrosine; C, IP control" provenance.
• _5 value "We have shown recently that Flt-1 VEGFR is expressed in the human MM cell line and patient MM cells and is tyrosine-phosphorylated upon VEGF stimulation (12). Because Flt-1 and the p85 subunit of PI 3-kinase were associated when overexpressed in yeast cells (54), we next determined whether this interaction is biologically significant in MM cells. Flt-1 was immunoprecipitated from VEGF treated and non-treated MM.1S cells followed by immunoblotting with anti-p85 Ab. As illustrated in Fig.5a, p85 is constitutively associated with Flt-1, suggesting that PI 3-kinase participates in Flt-1-mediated VEGF signal transduction." provenance.
• _5 value "We have shown recently that Flt-1 VEGFR is expressed in the human MM cell line and patient MM cells and is tyrosine-phosphorylated upon VEGF stimulation (12). Because Flt-1 and the p85 subunit of PI 3-kinase were associated when overexpressed in yeast cells (54), we next determined whether this interaction is biologically significant in MM cells. Flt-1 was immunoprecipitated from VEGF treated and non-treated MM.1S cells followed by immunoblotting with anti-p85 Ab. As illustrated in Fig.5a, p85 is constitutively associated with Flt-1, suggesting that PI 3-kinase participates in Flt-1-mediated VEGF signal transduction." provenance.
• _5 value "Here, we show that repetitive slow fiber type electrical stimulation, but not fast fiber type stimulation, caused HDAC4-GFP, but not HDAC5-GFP, to translocate from the nucleus to the cytoplasm in cultured adult skeletal muscle fibers. HDAC4-GFP translocation was blocked by calmodulin-dependent protein kinase (CaMK) inhibitor KN-62." provenance.
• _5 value "Here, we show that repetitive slow fiber type electrical stimulation, but not fast fiber type stimulation, caused HDAC4-GFP, but not HDAC5-GFP, to translocate from the nucleus to the cytoplasm in cultured adult skeletal muscle fibers. HDAC4-GFP translocation was blocked by calmodulin-dependent protein kinase (CaMK) inhibitor KN-62." provenance.
• _5 value "Slow fiber type stimulation increased MEF2 transcriptional activity, nuclear Ca2+ concentration, and nuclear levels of activated CaMKII, but not total nuclear CaMKII or CaM-YFP. Thus, calcium transients for slow, but not fast, fiber stimulation patterns appear to provide sufficient Ca2+-dependent activation of nuclear CaMKII to result in net nuclear efflux of HDAC4." provenance.
• _3 value "Slow fiber type stimulation increased MEF2 transcriptional activity, nuclear Ca2+ concentration, and nuclear levels of activated CaMKII, but not total nuclear CaMKII or CaM-YFP. Thus, calcium transients for slow, but not fast, fiber stimulation patterns appear to provide sufficient Ca2+-dependent activation of nuclear CaMKII to result in net nuclear efflux of HDAC4." provenance.
• _5 value "1 h of 10-Hz train stimulation significantly increased (P < 0.01) the mean nuclear stain of activated CaMKII compared with unstimulated fibers, and KN-62 (5 μM) blocked the increase in activated CaMKII staining after stimulation (Fig. 3 A). In parallel experiments, in which the fibers were stained with antibody directed against total CaMKII, there was no difference in mean nuclear antibody stain between stimulated and unstimulated fibers (P > 0.05; Fig. 3 A). These results are consistent with activation of nuclear CaMKII by fiber electrical stimulation without any appreciable translocation of CaMKII from the cytoplasm to the nucleus." provenance.
• _5 value "Over a 60-min period of treatment with 1 μM calyculin A (a PP1 and PP2A phosphatase inhibitor that does not affect PP2B; Ishihara et al., 1989), the nuclear HDAC4-GFP fluorescence decreased linearly with a mean net export rate of -0.71 ± 0.07%/min (Fig. 9 A, 13 nuclei from 5 fibers)." provenance.
• _5 value "Interestingly, calyculin A also caused a similar rate of efflux of HDAC5-GFP (-0.62 ± 0.05, nine nuclei from six fibers) from nuclei as observed for HDAC4, establishing the ability of HDAC5 to move out of the nucleus even though it did not translocate in response to electrical stimulation." provenance.
• _5 value "LPS + IFNγ caused an increase in monolayer permeability, induction of iNOS and NADPH oxidase type 1 (Nox1) proteins, formation of superoxide, nitric oxide and 3-nitrotyrosine, and increase in PP2A activity in endothelial cells. These effects of LPS + IFNγ were diminished by tripterine (50-200 nM)." provenance.

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