scholarly journals Phospholipase C gamma complexes with ligand-activated platelet-derived growth factor receptors. An intermediate implicated in phospholipase activation

1991 ◽  
Vol 266 (6) ◽  
pp. 3973-3980 ◽  
Author(s):  
D A Kumjian ◽  
A Barnstein ◽  
S G Rhee ◽  
T O Daniel
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Growth Factor Receptors ◽  
Platelet Derived Growth Factor ◽  
Phospholipase C Gamma

scholarly journals Phosphorylation and activation of epidermal growth factor receptors in cells transformed by the src oncogene.

1991 ◽  
Vol 11 (1) ◽  
pp. 309-321 ◽  
Author(s):  
W J Wasilenko ◽  
D M Payne ◽  
D L Fitzgerald ◽  
M J Weber
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Egf Receptor ◽  
Growth Factor Receptors ◽  
Epidermal Growth ◽  
Phospholipase C Gamma ◽  
Signaling Activity ◽  
In Cells

Because functionally significant substrates for the tyrosyl protein kinase activity of pp60v-src are likely to include membrane-associated proteins involved in normal growth control, we have tested the hypothesis that pp60v-src could phosphorylate and alter the signaling activity of transmembrane growth factor receptors. We have found that the epidermal growth factor (EGF) receptor becomes constitutively phosphorylated on tyrosine in cells transformed by the src oncogene and in addition displays elevated levels of phosphoserine and phosphothreonine. High-performance liquid chromatography phosphopeptide mapping revealed two predominant sites of tyrosine phosphorylation, both of which differed from the major sites of receptor autophosphorylation; thus, the src-induced phosphorylation is unlikely to occur via an autocrine mechanism. To determine whether pp60v-src altered the signaling activity of the EGF receptor, we analyzed the tyrosine phosphorylation of phospholipase C-gamma, since phosphorylation of this enzyme occurs in response to activation of the EGF receptor but not in response to pp60v-src alone. We found that in cells coexpressing pp60v-src and the EGF receptor, phospholipase C-gamma was constitutively phosphorylated, a result we interpret as indicating that the signaling activity of the EGF receptor was altered in the src-transformed cells. These findings suggest that pp60v-src-induced alterations in phosphorylation and function of growth regulatory receptors could play an important role in generating the phenotypic changes associated with malignant transformation.

scholarly journals Demonstration of Functionally Different Interactions between Phospholipase C-γ and the Two Types of Platelet-derived Growth Factor Receptors

1995 ◽  
Vol 270 (13) ◽  
pp. 7773-7781 ◽  
Author(s):  
Anders Eriksson ◽  
Eewa Nånberg ◽  
Lars Rönnstrand ◽  
Ulla Engström ◽  
Ulf Hellman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Growth Factor Receptors ◽  
Platelet Derived Growth Factor

Platelet-derived growth factor increases the in vivo activity of phospholipase C-gamma 1 and phospholipase C-gamma 2

1991 ◽  
Vol 11 (4) ◽  
pp. 2018-2025
Author(s):  
L Sultzman ◽  
C Ellis ◽  
L L Lin ◽  
T Pawson ◽  
J Knopf
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Cell Surface Receptor ◽  
Platelet Derived Growth Factor ◽  
Surface Receptor ◽  
Phospholipase C Gamma

Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of diacylglycerol and inositol 1,4,5-triphosphate. We showed that following stimulation by PDGF, rat-2 cells overexpressing PLC-gamma 1 display an increase in the levels of both tyrosine-phosphorylated PLC-gamma 1 and inositol phosphates compared with the parental rat-2 cells. This increased responsiveness to PDGF is a direct effect of PLC-gamma 1 overexpression, as a cell line expressing similar levels of an enzymatically inactive point mutant of PLC-gamma 1, PLC-gamma 1 335Q, did not show elevated inositol phosphate production in response to PDGF. Hematopoietic cells express PLC-gamma 2, a PLC isoform that is closely related to PLC-gamma 1. When rat-2 cells overexpressing PLC-gamma 2 were treated with PDGF, an increase in both the tyrosine phosphorylation and the in vivo activity of PLC-gamma 2 was observed. Aluminum fluoride (AIF4-), a universal activator of PLC linked to G-proteins, did not produce an increase in the levels of inositol phosphates in either of the overexpressing cell lines compared with parental rat-2 cells, demonstrating that PLC-gamma isoforms respond specifically to a receptor with tyrosine kinase activity.

Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors

Science ◽  
1990 ◽  
Vol 250 (4983) ◽  
pp. 979-982 ◽  
Author(s):  
D Anderson ◽  
C. Koch ◽  
L Grey ◽  
C Ellis ◽  
M. Moran ◽  
...  
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Growth Factor Receptors ◽  
Sh2 Domains ◽  
Phospholipase C Gamma

scholarly journals Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor.

1990 ◽  
Vol 10 (11) ◽  
pp. 6069-6072 ◽  
Author(s):  
A Cuadrado ◽  
C J Molloy
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Phosphoinositide Metabolism ◽  
Fibroblast Growth ◽  
3T3 Fibroblasts ◽  
Phospholipase C Gamma ◽  
Nih 3T3

Overexpression of phospholipase C-gamma in fibroblasts led to increased tyrosine phosphorylation of this enzyme in response to platelet-derived growth factor and basic fibroblast growth factor. This correlated with increased phosphoinositide release but not with enhanced mitogenicity. Thus, phospholipase C-gamma-mediated phosphoinositide metabolism may not be limiting in the signaling pathways initiated by these growth factors.

Overexpression of phospholipase C-gamma in NIH 3T3 fibroblasts results in increased phosphatidylinositol hydrolysis in response to platelet-derived growth factor and basic fibroblast growth factor

1990 ◽  
Vol 10 (11) ◽  
pp. 6069-6072
Author(s):  
A Cuadrado ◽  
C J Molloy
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Phosphoinositide Metabolism ◽  
Fibroblast Growth ◽  
3T3 Fibroblasts ◽  
Phospholipase C Gamma ◽  
Nih 3T3

Overexpression of phospholipase C-gamma in fibroblasts led to increased tyrosine phosphorylation of this enzyme in response to platelet-derived growth factor and basic fibroblast growth factor. This correlated with increased phosphoinositide release but not with enhanced mitogenicity. Thus, phospholipase C-gamma-mediated phosphoinositide metabolism may not be limiting in the signaling pathways initiated by these growth factors.

scholarly journals Platelet-derived growth factor increases the in vivo activity of phospholipase C-gamma 1 and phospholipase C-gamma 2.

1991 ◽  
Vol 11 (4) ◽  
pp. 2018-2025 ◽  
Author(s):  
L Sultzman ◽  
C Ellis ◽  
L L Lin ◽  
T Pawson ◽  
J Knopf
Keyword(s):  
Growth Factor ◽  
Phospholipase C ◽  
Tyrosine Phosphorylation ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Cell Surface Receptor ◽  
Platelet Derived Growth Factor ◽  
Surface Receptor ◽  
Phospholipase C Gamma

Upon binding to its cell surface receptor, platelet-derived growth factor (PDGF) causes the tyrosine phosphorylation of phospholipase C-gamma 1 (PLC-gamma 1) and stimulates the production of diacylglycerol and inositol 1,4,5-triphosphate. We showed that following stimulation by PDGF, rat-2 cells overexpressing PLC-gamma 1 display an increase in the levels of both tyrosine-phosphorylated PLC-gamma 1 and inositol phosphates compared with the parental rat-2 cells. This increased responsiveness to PDGF is a direct effect of PLC-gamma 1 overexpression, as a cell line expressing similar levels of an enzymatically inactive point mutant of PLC-gamma 1, PLC-gamma 1 335Q, did not show elevated inositol phosphate production in response to PDGF. Hematopoietic cells express PLC-gamma 2, a PLC isoform that is closely related to PLC-gamma 1. When rat-2 cells overexpressing PLC-gamma 2 were treated with PDGF, an increase in both the tyrosine phosphorylation and the in vivo activity of PLC-gamma 2 was observed. Aluminum fluoride (AIF4-), a universal activator of PLC linked to G-proteins, did not produce an increase in the levels of inositol phosphates in either of the overexpressing cell lines compared with parental rat-2 cells, demonstrating that PLC-gamma isoforms respond specifically to a receptor with tyrosine kinase activity.

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