The tyrosine kinase src regulates activation of phospholipase C gamma and opening of potassium and chloride channels in response to hepatocellular swelling

2003 ◽  
Vol 124 (4) ◽  
pp. A693
Author(s):  
Richard F. Melnick ◽  
Ann L. Moore ◽  
Elisabeth T. Barfod ◽  
Steven D. Lidofsky
Keyword(s):  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Chloride Channels ◽  
Phospholipase C Gamma

scholarly journals Transfection of Syk protein tyrosine kinase reconstitutes high affinity IgE receptor-mediated degranulation in a Syk-negative variant of rat basophilic leukemia RBL-2H3 cells.

1996 ◽  
Vol 184 (1) ◽  
pp. 71-79 ◽  
Author(s):  
J Zhang ◽  
E H Berenstein ◽  
R L Evans ◽  
R P Siraganian
Keyword(s):  
Tyrosine Kinase ◽  
Histamine Release ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Kinase ◽  
Immunoglobulin E ◽  
Critical Role ◽  
Protein Tyrosine ◽  
High Affinity ◽  
Phospholipase C Gamma

Aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells results in rapid tyrosine phosphorylation and activation of Syk, a cytoplasmic protein tyrosine kinase. To examine the role of Syk in the Fc epsilon RI signaling pathway, we identified a variant of RBL-2H3 cells that has no detectable Syk by immunoblotting and by in vitro kinase reactions. In these Syk-deficient TB1A2 cells, aggregation of Fc epsilon RI induced no histamine release and no detectable increase in total cellular protein tyrosine phosphorylation. However, stimulation of these cells with the calcium ionophore did induce degranulation. Fc epsilon RI aggregation induced tyrosine phosphorylation of the beta and gamma subunits of the receptor, but no increase in the tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2 and no detectable increase in intracellular free Ca2+ concentration. By transfection, cloned lines were established with stable expression of Syk. In these reconstituted cells, Fc epsilon RI aggregation induced tyrosine phosphorylation of phospholipase C-gamma 1 and phospholipase C-gamma 2, an increase in intracellular free Ca2+ and histamine release. These results demonstrate that Syk plays a critical role in the early Fc epsilon RI-mediated signaling events. It further demonstrates that Syk activation occurs downstream of receptor phosphorylation, but upstream of most of the Fc epsilon RI-mediated protein tyrosine phosphorylations.

scholarly journals Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase.

1990 ◽  
Vol 10 (9) ◽  
pp. 4770-4777 ◽  
Author(s):  
W H Burgess ◽  
C A Dionne ◽  
J Kaplow ◽  
R Mudd ◽  
R Friesel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Receptor Activation ◽  
Cdna Clones ◽  
Heparin Binding ◽  
Acidic Fibroblast Growth Factor ◽  
Intact Cells ◽  
Surface Receptors ◽  
Phospholipase C Gamma

Heparin-binding growth factors (HBGFs) bind to high-affinity cell surface receptors which possess intrinsic tyrosine kinase activity. A Mr 150,000 protein phosphorylated on tyrosine in response to class 1 HBGF (HBGF-1) was purified and partially sequenced. On the basis of this sequence, cDNA clones were isolated from a human endothelial cell library and identified as encoding phospholipase C-gamma. Phosphorylation of phospholipase C-gamma in intact cells treated with HBGF-1 was directly demonstrated by using antiphospholipase C-gamma antibodies. Thus, HBGF-1 joins epidermal growth factor and platelet-derived growth factor, whose receptor activation leads to tyrosine phosphorylation and probable activation of phospholipase C-gamma.

scholarly journals Oncogenic forms of the neu/HER2 tyrosine kinase are permanently coupled to phospholipase C gamma.

1991 ◽  
Vol 10 (8) ◽  
pp. 2077-2086 ◽  
Author(s):  
E. Peles ◽  
R.B. Levy ◽  
E. Or ◽  
A. Ullrich ◽  
Y. Yarden
Keyword(s):  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Phospholipase C Gamma

scholarly journals Association of protein-tyrosine kinase with phospholipase C-gamma 1 in bone marrow-derived mouse mast cells.

1992 ◽  
Vol 89 (20) ◽  
pp. 9524-9528 ◽  
Author(s):  
H. Fukamachi ◽  
Y. Kawakami ◽  
M. Takei ◽  
T. Ishizaka ◽  
K. Ishizaka ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Protein Tyrosine Kinase ◽  
Protein Tyrosine ◽  
Phospholipase C Gamma

scholarly journals Activation of phospholipase C gamma in Schizosaccharomyces pombe by coexpression of receptor or nonreceptor tyrosine kinases.

1995 ◽  
Vol 15 (3) ◽  
pp. 1431-1438 ◽  
Author(s):  
S Arkinstall ◽  
M Payton ◽  
K Maundrell
Keyword(s):  
Tyrosine Kinase ◽  
Schizosaccharomyces Pombe ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Cell System ◽  
Negative Regulator ◽  
Nonreceptor Tyrosine Kinase ◽  
Beta Receptor ◽  
Phospholipase C Gamma

The fission yeast Schizosaccharomyces pombe has no detectable endogenous receptor tyrosine kinases or associated signalling apparatus, and we have used this cell system to reconstitute mammalian platelet-derived growth factor beta (PDGF beta) receptor-linked activation of phospholipase C gamma 2 (PLC gamma 2). The PDGF beta receptor migrates as a glycosylated protein of 165 kDa associated exclusively with membrane fractions. No tyrosine autophosphorylation was detected when PDGF beta was expressed alone. PLC gamma 2 appears as a 140-kDa protein distributed between particulate and soluble fractions which exhibits characteristic selectivity for phosphatidylinositol 4,5-bisphosphate and is sensitive to powerful activation by Ca2+. When coexpressed, both PDGF beta and PLC gamma 2 undergo tyrosine phosphorylation, and this is accompanied by a > 26-fold increase in [3H]inositol 4,5-biphosphate ([3H]IP2) and [3H]inositol 1,4,5-triphosphate [3H]IP3 production. Treatment with the tyrosine phosphatase inhibitor pervanadate further increased PLC gamma 2 tyrosine phosphorylation as well as [3H]IP2 and [3H]IP3 generation. Phosphorylated PLC gamma 2 was found predominantly in membrane fractions. To test a nonreceptor tyrosine kinase, we then expressed the human proto-oncogene c-src together with its negative regulator Csk. These were immunodetectable as bands at 60 kDa (c-Src) and 50 kDa (Csk) and distributed between membrane and cytosolic fractions. When yeast coexpressing c-Src, Csk, and PLC gamma 2 was incubated with pervanadate, PLC gamma 2 was tyrosine phosphorylated and [3H]IP2 and [3H]IP3 production increased 11.0- and 7.0-fold, respectively. Csk expressed alone with PLC gamma 2 was ineffective. Similar PLC gamma 2 activation was observed upon in vitro mixing with the extracts expressing either c-Src or the PDGF beta receptor. In summary, this is the first report of a reconstitution of mammalian tyrosine kinase-linked effector activation in yeast cells and also the first demonstration of direct PLC gamma 2 activation by the proto-oncogene c-src. These observations indicate that S. pombe provides a powerful cell system in which to study critical molecular interactions and activities underlying receptor and nonreceptor tyrosine kinase-dependent cell signaling.

Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase

1990 ◽  
Vol 10 (9) ◽  
pp. 4770-4777
Author(s):  
W H Burgess ◽  
C A Dionne ◽  
J Kaplow ◽  
R Mudd ◽  
R Friesel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinase ◽  
Phospholipase C ◽  
Receptor Activation ◽  
Cdna Clones ◽  
Heparin Binding ◽  
Acidic Fibroblast Growth Factor ◽  
Intact Cells ◽  
Surface Receptors ◽  
Phospholipase C Gamma

Heparin-binding growth factors (HBGFs) bind to high-affinity cell surface receptors which possess intrinsic tyrosine kinase activity. A Mr 150,000 protein phosphorylated on tyrosine in response to class 1 HBGF (HBGF-1) was purified and partially sequenced. On the basis of this sequence, cDNA clones were isolated from a human endothelial cell library and identified as encoding phospholipase C-gamma. Phosphorylation of phospholipase C-gamma in intact cells treated with HBGF-1 was directly demonstrated by using antiphospholipase C-gamma antibodies. Thus, HBGF-1 joins epidermal growth factor and platelet-derived growth factor, whose receptor activation leads to tyrosine phosphorylation and probable activation of phospholipase C-gamma.

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