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

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serine-threonine protein kinase Raf-1 is an important signal transducer in mitogenesis, phosphorylating and activating mitogen-activated protein (MAP) kinase kinase. Raf-1 activation in vivo is dependent on Ras, but the mechanism of Raf activation is unknown. The ability of preparations of plasma membranes to activate exogenous (His)6-Raf-1 was studied. Plasma membranes of v-Ras-transformed NIH 3T3 cells, but not parental cells, enhanced MAP kinase kinase kinase (MAPKKK) activity dependent on addition of (His)6-Raf-1 and ATP/Mg. Treatment of membranes with concentrations of Bacillus cereus phosphatidylcholine-specific phospholipase C that activated Raf-1 in vivo failed to enhance MAPKKK activity in vitro. Activation of (His)6-Raf-1 in vitro by membranes was dependent on binding to Ras. Membranes from v-Src-transformed cells also activated (His)6-Raf-1 and synergized with v-Ras membranes. Serum-treatment of NIH 3T3 cells stimulated the ability of membranes to activate (His)6-Raf-1. Activated (His)6-Raf-1 could be recovered on Ni(2+)-agarose, and this methodology was used to demonstrate that activation by membranes was ATP dependent. These findings demonstrate Ras- and ATP-dependent step(s) for Raf-1 activation by plasma membranes in vitro.
...
PMID:Activation of (His)6-Raf-1 in vitro by partially purified plasma membranes from v-Ras-transformed and serum-stimulated fibroblasts. 793 2

Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are cytokines with pleiotropic biological activities, exerting a broad range of overlapping biological functions. The redundancy of TNF and IL-1 activities may be based on the utilization of shared key components of intracellular signaling pathways. Two lipid second messengers have been found to transmit TNF and IL-1 intracellular signals: 1,2-diacylglycerol (DAG), generated by a phosphatidylcholine-specific phospholipase C, and ceramide, generated by sphingomyelinase (SMase). DAG is a well established activator of the important signaling system protein kinase C (PKC), which appears to mediate various cellular responses to TNF or IL-1. In addition, it is obvious that DAG also activates other enzyme systems like acidic sphingomyelinase. SMases have been implicated in a number of TNF responses, including stimulation of cell growth and differentiation, as well as triggering cytotoxicity and apoptosis. The metabolic active cleavage product of SMase, ceramide, is a novel multifunctional lipid second messenger capable of inducing various signaling systems. Both cytokines, TNF and IL-1, stimulate a neutral,plasma membrane-associated SMase that leads to stimulation of a protein kinase and eventually to activation of the mitogen-activated protein (MAP) kinase cascade and phospholipase A2. Ceramide is also capable of stimulating a cytosolic protein phosphatase. PKC plays a role in activation of the nuclear transcription factor AP-1, and the DAG-regulated acidic SMase is involved in transducing TNF signals to the cell nucleus via activation of the nuclear transcription factor NF-kappa B.
...
PMID:The role of diacylglycerol and ceramide in tumor necrosis factor and interleukin-1 signal transduction. 796 60

The present study was undertaken to determine whether extracellular ATP promotes cellular growth of glomerular mesangial cells. ATP increased inositol 1,4,5-trisphosphate (IP3) production and cellular free calcium concentration ([Ca2+]i) in a dose-dependent manner. None of ADP, AMP or adenosine caused an increase in IP3 production or [Ca2+]i mobilization. Also, ATP activated mitogen-activated protein (MAP) kinase and 3H-thymidine incorporation and increased the absorbance by colorimetric assay in a dose-dependent manner. Again, either of ADP, AMP or adenosine had no effect. These results indicate that extracellular ATP binds to P2 purinergic receptors and activates phospholipase C in glomerular mesangial cells. Such a signal transduction promotes cellular growth of mesangium.
...
PMID:Extracellular ATP promotes cellular growth of glomerular mesangial cells mediated via phospholipase C. 803 16

Activation of mitogen-activated protein kinases (MAPKs) was examined in the A7r5 rat vascular smooth muscle cell line. Treatment of A7r5 cells with vasopressin, phorbol ester (PMA), or serum resulted in activation of two MAPKs, Erk-1 and Erk-2. Phosphatidylinositol-specific phospholipase C was activated in response to vasopressin but not to PMA. Vasopressin and PMA both caused maximal activation of PLD within 5 minutes. Application of bacterial phospholipase D (PLD) to A7r5 cells increased phosphatidic acid to levels similar to those seen with vasopressin or PMA. Acute exposure of the cells to vasopressin, PMA, or PLD increased phosphorylation of many of the same cytosolic and membrane proteins. However, bacterial PLD did not promote significant activation of Erk-1 and Erk-2. Phosphatidic acid and lysophosphatidic acid (LPA) likewise did not stimulate MAPK activity in A7r5 cells. Serum and vasopressin stimulated DNA synthesis when present for more than 30 min, while PLD, PMA, phosphatidic acid, and LPA were not mitogenic. These data suggest that activations of MAPKs and PLD are concurrent but independent responses to vasopressin in A7r5 cells. Acute activation of these enzymes is not sufficient to simulate DNA synthesis.
...
PMID:Activations of mitogen-activated protein kinases and phospholipase D in A7r5 vascular smooth muscle cells. 808 51

Arginine vasopressin (AVP) has been shown to stimulate tyrosine phosphorylation and activation of p42 mitogen-activated protein (MAP) kinase (p42MAPK) in vascular smooth muscle cells (VSMC). In VSMC, AVP increases free intracellular Ca2+ concentration ([Ca2+]i) and activates protein kinase C (PKC) through activation of phospholipase C. The contribution of PKC and [Ca2+]i in p42MAPK regulation was therefore determined. Activation of PKC by phorbol 12-myristate 13-acetate (PMA) stimulated tyrosine phosphorylation and activation of p42MAPK to the same extent as AVP. Inhibition of PKC by staurosporine or downregulation of PKC by PMA pretreatment abolished AVP-induced stimulation of p42MAPK. When [Ca2+]i was elevated to the same level as with AVP, using either ionomycin (0.1 microM) or thapsigargin (0.1 microM), MAP kinase was only partially activated. Elevation of [Ca2+]i to supraphysiological levels by 1 microM ionomycin stimulated MAP kinase activity to the same extent as AVP. This effect was blocked by downregulation of PKC. The intracellular Ca2+ chelator BAPTA [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked AVP-induced [Ca2+]i increase but did not affect AVP stimulation of p42MAPK. Thus AVP-induced activation of p42MAPK requires only the activation of PKC but not an increase in [Ca2+]i.
...
PMID:AVP-induced activation of MAP kinase in vascular smooth muscle cells is mediated through protein kinase C. 823 19

Lysophosphatidic acid (LPA) is a platelet-derived phospholipid that serves as a mitogen for fibroblasts. LPA activates its own G protein-coupled receptor(s) leading to stimulation of phospholipase C and inhibition of adenylate cyclase. Furthermore, LPA rapidly activates p21ras through a pertussis toxin-sensitive pathway. In this study, we have examined LPA-induced protein tyrosine phosphorylation in Rat-1 fibroblasts. LPA action was compared with that of endothelin, which is a stronger activator of phospholipase C than LPA but fails to activate p21ras and to stimulate DNA synthesis in these cells. LPA and, more effectively, endothelin rapidly stimulate tyrosine phosphorylation of proteins of 110-130, 95, and 65-75 kDa. The effect of LPA is dose- and time-dependent, being half-maximal at 3-30 nM and peaking after 2-5 min. Among the 110-130-kDa group of phosphotyrosyl proteins is the 125-kDa "focal adhesion kinase" (p125FAK) but not the 120-kDa p21ras GTPase-activating protein. Furthermore, LPA, like epidermal growth factor, causes tyrosine phosphorylation and activation of the p42/p44 mitogen-activated protein (MAP) kinases, paralleling p21ras activation. In contrast, endothelin fails to phosphorylate MAP kinase. Treatment of the cells with pertussis toxin blocks LPA-induced MAP kinase phosphorylation without affecting the other tyrosine phosphorylations. The kinase inhibitor staurosporine (1 microM) blocks LPA-induced, but not epidermal growth factor-induced, activation of p21ras and MAP kinase, consistent with an intermediate protein kinase linking the LPA receptor to p21ras activation. The results support a model in which LPA-induced phosphorylation of MAP kinase is mediated by p21ras, and tyrosine phosphorylation of the other substrates, including p125FAK, is associated with phospholipase C activation.
...
PMID:Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1 fibroblasts. Evidence that phosphorylation of map kinase is mediated by the Gi-p21ras pathway. 827 65

It is well known that external load plays a critical role in determining cardiac muscle mass and its phenotype, but little is known as to how mechanical load is transduced into intracellular signals regulating gene expression. To address this question we analyzed the 'mechano-transcription' coupling process using an in vitro model of load-induced cardiac hypertrophy, in which a stretch of rat cardiac myocytes, grown on a deformable substrate, causes a rapid induction of immediate-early genes followed by growth (hypertrophic) response. We report here that cell stretch rapidly activates a plethora of second messenger pathways, including tyrosine kinases, p21ras, mitogen-activated protein (MAP) kinases, S6 kinases (pp90RSK), protein kinase C, phospholipase C, phospholipase D, and probably the phospholipase A2 and P450 pathways. In contrast, the cAMP pathway is not activated significantly by stretch. The signals generated by these second messengers appear to converge into activation of the p67SRF-p62TCF complex via the serum response element, causing induction of c-fos. The stretch response may involve an autocrine or paracrine mechanism, because stretch-conditioned medium, when transferred to non-stretched myocytes, mimicked the effect of stretch. These results indicate that mechanical load causes rapid activation of multiple second messenger systems, which may in turn initiate a cascade of hypertrophic response of cardiac myocytes.
...
PMID:Mechanical stretch rapidly activates multiple signal transduction pathways in cardiac myocytes: potential involvement of an autocrine/paracrine mechanism. 838 10

Persistent stimulation of specific protein kinase pathways has been proposed as a key feature of receptor tyrosine kinases and intracellular oncoproteins that signal neuronal differentiation of rat pheochromocytoma (PC12) cells. Among the protein serine/threonine kinases identified to date, the p42/44 mitogen-activated protein (MAP) kinases have been highlighted for their potential role in signalling PC12 cell differentiation. We report here that retrovirus-mediated expression of GTPase-deficient, constitutively active forms of the heterotrimeric Gq family members, G alpha qQ209L and G alpha 16Q212L, in PC12 cells induces neuronal differentiation as indicated by neurite outgrowth and the increased expression of voltage-dependent sodium channels. Differentiation was not observed after cellular expression of GTPase-deficient forms of alpha i2 or alpha 0, indicating selectivity for the Gq family of G proteins. As predicted, overexpression of alpha qQ209L and alpha 16Q212L constitutively elevated basal phospholipase C activity approximately 10-fold in PC12 cells. Significantly, little or no p42/44 MAP kinase activity was detected in PC12 cells differentiated with alpha 16Q212L or alpha qQ209L, although these proteins were strongly activated following expression of constitutively active cRaf-1. Rather, a persistent threefold activation of the cJun NH2-terminal kinases (JNKs) was observed in PC12 cells expressing alpha qQ209L and alpha 16Q212L. This level of JNK activation was similar to that achieved with nerve growth factor, a strong inducer of PC12 cell differentiation. Supportive of a role for JNK activation in PC12 cell differentiation, retrovirus-mediated overexpression of cJun, a JNK target, in PC12 cells induced neurite outgrowth. The results define a p42/44 MAP kinase-independent mechanism for differentiation of PC12 cells and suggest that persistent activation of the JNK members of the proline-directed protein kinase family by GTPase-deficient G alpha q and G alpha 16 subunits is sufficient to induce differentiation of PC12 cells.
...
PMID:GTPase-deficient G alpha 16 and G alpha q induce PC12 cell differentiation and persistent activation of cJun NH2-terminal kinases. 855 93

Cardiac fibroblasts appear to be important in producing and maintaining the extracellular matrix (ECM) of the heart. The abnormal proliferation of cardiac fibroblasts and deposition of the ECM protein, collagen, associated with hypertension and myocardial infarction, may adversely affect the performance of the heart. Several groups of factors affect collagen gene expression and/or growth of cardiac fibroblasts. Angiotensin II, aldosterone and endothelins play a central role in the remodeling of the ECM in hypertension, and decrease collagenase activity and/or increase collagen synthesis in cultured cells. Regulatory peptides that are generally elevated at sites of injury, such as TGF-beta 1 and PDGF, increase collagen synthesis and/or stimulate mitogenesis. Mechanical stretch enhances collagen expression and cell proliferation, responses which could in part be due to integrin activation. Cytokines may stimulate or inhibit cell growth, the latter through prostaglandin formation. Angiotensin II is a principal determinant in vivo of cardiac fibroplasia and synthesis of the ECM proteins, collagen and fibronectin. Cardiac fibroblasts possess G-protein-coupled AT1 receptors for angiotensin II that couple to activation of multiple signalling pathways, including: phospholipase C-beta, with the subsequent release of Ca2+ from intracellular stores and activation of protein kinase C, mitogen-activated protein kinases, tyrosine kinases, phospholipase D, phosphatidic acid formation, and the STAT family of transcription factors. Cardiac fibroblasts respond to angiotensin II with hyperplastic/hypertrophic growth, and increased expression of collagen, fibronectin, and integrins. The mechanisms by which the AT1 receptor activates multiple signalling pathways are not known, although the receptor might interact at some level with both integrins and cytokine receptors. Different signalling pathways of the AT1 receptor may subserve different cellular responses, such as mitogenesis, ECM synthesis, or an inflammatory/stress response. Crosstalk among the signalling pathways of the AT1 receptor, and those of G-protein, cytokine, and growth-factor receptors, may determine the ultimate response of the cell.
...
PMID:Molecular signalling mechanisms controlling growth and function of cardiac fibroblasts. 857 2

The exchange of nerve growth factor receptor/Trk and epidermal growth factor receptor (EGFR) phospholipase C gamma (PLC gamma) binding sites resulted in the transfer of their distinct affinities for this Src homology 2 domain-containing protein. Relative to wild-type EGFR, the PLC gamma affinity increase of the EGFR switch mutant EGFR.X enhanced its inositol trisphosphate (IP3) and calcium signals and resulted in a more sustained mitogen-activated protein (MAP) kinase activation and accelerated receptor dephosphorylation. In parallel, EGFR.X exhibited a significantly decreased mitogenic and transforming potential in NIH 3T3 cells. Conversely, the transfer of the EGFR PLC gamma binding site into the Trk cytoplasmic domain context impaired the IP3/calcium signal and attenuated the MAP kinase activation and receptor dephosphorylation, but resulted in an enhancement of the ETR.X exchange mutant mitogenic and oncogenic capacity. Our findings establish the significance of PLC gamma affinity for signal definition, the role of this receptor tyrosine kinase substrate as a negative feedback regulator and the importance of this regulatory function for mitogenesis and its disturbance in oncogenic aberrations.
...
PMID:Transforming potentials of epidermal growth factor and nerve growth factor receptors inversely correlate with their phospholipase C gamma affinity and signal activation. 859 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---