1,25 dihydroxyvitamin D3 stimulates phospholipase C-gamma in rat colonocytes: role of c-Src in PLC-gamma activation.

Khare, Sharad; Bolt, Merry J.G.; Wali, Ramesh K.; Skarosi, S.; Roy, Hemant K.; Niedziela, Sharon M.; Scaglione-Sewell, B.; Aquino, Bruna de Melo; Abraham, Clara; Sitrin, Michael D.; Brasitus, Thomas A.; Bissonnette, Marc

doi:10.1172/jci119350

Cited by 68 publications

(48 citation statements)

References 41 publications

(55 reference statements)

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“…This possibility appears plausible because both PLC␥1 and the AT 1 receptor have been shown previously to be excellent substrates for Src kinases in vitro (13,16). Furthermore, PLC␥1 has been shown to form a complex with c-Src in several other cell types (7,17,18). An alternative explanation for the inhibitory effect of PP1 is that Src kinase activity may be required for a phosphorylation event that is upstream from either PLC␥1 or AT 1 receptor phosphorylation in a tyrosine phosphorylation cascade.…”

Section: Resultsmentioning

confidence: 90%

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Venema

et al. 1998

Journal of Biological Chemistry

101

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An early event in signaling by the G-protein-coupled angiotensin II (Ang II) AT 1 receptor in vascular smooth muscle cells is the tyrosine phosphorylation and activation of phospholipase C␥1 (PLC␥1). In the present study, we show that stimulation of this event by Ang II in vascular smooth muscle cells is accompanied by binding of PLC␥1 to the AT 1 receptor in an Ang II-and tyrosine phophorylation-dependent manner. The PLC␥1-AT 1 receptor interaction appears to depend on phosphorylation of tyrosine 319 in a YIPP motif in the C-terminal intracellular domain of the AT 1 receptor and binding of the phosphorylated receptor by the most C-terminal of two Src homology 2 domains in PLC␥1. PLC␥1 thus binds to the same site in the receptor previously identified for binding by the SHP-2 phosphotyrosine phosphatase⅐JAK2 tyrosine kinase complex. A single site in the C-terminal tail of the AT 1 receptor can, therefore, be bound in a ligand-dependent manner by two different downstream effector proteins. These data demonstrate that G-protein-coupled receptors can physically associate with intracellular proteins other than G proteins, creating membrane-delimited signal transduction complexes similar to those observed for classic growth factor receptors.Growth factor receptors belong to a family of receptors that contain an extracellular ligand binding domain, a single transmembrane portion, and a large intracellular tyrosine kinase catalytic domain. Ligand-induced receptor autophosphorylation promotes the interaction of the intracellular domains of the receptors with a number of downstream effector proteins or enzymes. Typically, these proteins contain one or more domains known as Src homology 2 (SH2) 1 domains. Among these SH2 domain-containing proteins are phosphoinositide-specific phospholipase C␥ (PLC␥), the 85-kDa subunit of phosphatidylinositol 3-kinase, GTPase-activating proteins, growth factor receptor binding protein 2, the phosphotyrosine phosphatase SHP-2, and members of the nonreceptor Src family of tyrosine kinases (1, 2). Autophosphorylation of growth factor receptors occurs on defined tyrosine residues. These phosphorylated residues function to initiate cellular signaling cascades by acting as high affinity binding sites for the SH2 domains of various effector proteins. The selectivity of the receptor-effector interaction is determined, not only by the phosphorylated tyrosine residue in the receptor but also by the three amino acids Cterminal to the phosphorylated tyrosine and by the structure of the SH2 domain of the interacting protein. For example, one of the identified sites for binding of the SH2 domains of PLC␥1 to the platelet-derived growth factor ␣ and ␤ receptors is a YIPP motif present in the receptors at residues 1018 -1021 and 1021-1024, respectively. Phosphorylation of tyrosines 1018 and 1021 in these motifs promotes binding of PLC␥1 to the platelet-derived growth factor receptor and tyrosine phosphorylation and activation of the enzyme (3, 4).Another family of cell surface receptors are the G-protein...

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Section: Resultsmentioning

confidence: 90%

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Venema

et al. 1998

Journal of Biological Chemistry

101

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“…Since our results show that in our cells PLC-g-1 is insensitive to EGF treatment, other mechanisms must be responsible for the permanent activation found in E5 cells. In this context it should be mentioned that in several cell systems, src-kinase can also be involved in the activation of PLC-g-1 activity (Khare et al, 1997;Reynolds et al, 1993;Singer et al, 1997). At this stage, however, whether this enhanced activation is the result of increased phosphorylation in an E5-dependent manner or an impaired PLC-g-1-speci®c phosphatase remains to be demonstrated.…”

Section: Discussionmentioning

confidence: 99%

The human papillomavirus type 16 E5 protein modulates phospholipase C-γ-1 activity and phosphatidyl inositol turnover in mouse fibroblasts

et al. 1999

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The human papillomavirus type 16 E5 (HPV16-E5) protein is a membrane protein that has been associated with malignant growth. The protein aects growth factor-mediated signal transduction in a ligand-dependent manner. We show now that E5 expression in A31 ®broblasts results in an increased level of diacylglycerol (DAG) and inositol phosphates. Immunoprecipitation of phospholipase C-g-1 (PLC-g-1) with speci®c antibodies and immunoblotting with anti-phosphotyrosine antibodies reveal a large increase in tyrosine phosphorylation of the enzyme in E5-expressing cells compared to control vector-transfected cells. This activation of tyrosine phosphorylation is growth factor independent. In addition, an enhanced formation of phosphatidic acid (PA) was observed in E5 cells. This increase did not result from activation of phospholipase D (PLD), although the enzyme was activatable by treatment with phorbol ester. Thus, a phosphohydrolase-mediated DAG synthesis from PLD-produced PA can be excluded. The observed eects were not further enhanced by EGF showing that the presence of the growth factor is not necessary for maintaining permanent activation of PLC-g-1 in E5-expressing cells. The DAG-and inositol phosphatemediated signal cascade within the cells is thus eectively uncoupled from external control via EGF and its receptor in the presence of E5 protein.

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“…These findings suggest a role for EGFR, but not PDGFR in mediating PLC-␥1 phosphorylation by oxidative stress. Previous studies have shown that Src family tyrosine kinases are involved in signaling events stimulated by reactive oxygen species (22)(23)(24) and Src kinase family members have also been demonstrated to phosphorylate PLC-␥1 and PLC-␥2 in vitro (25,26). To address the role of Src family kinases in H 2 O 2 -mediated phosphorylation of PLC-␥1, we utilized the selective Src family tyrosine kinase inhibitor PP2.…”

Section: H 2 O 2 Stimulates Tyrosine Phosphorylation Of Plc-␥1-mentioning

confidence: 99%

Oxidative Stress-induced Phospholipase C-γ1 Activation Enhances Cell Survival

Wang¹,

McCullough²,

Wang³

et al. 2001

Journal of Biological Chemistry

140

104

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Phospholipase C-␥1 (PLC-␥1) is rapidly activated in response to growth factor stimulation and plays an important role in regulating cell proliferation and differentiation through the generation of the second messengers diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C (PKC) and increased levels of intracellular calcium, respectively. Given the existing overlap between signaling pathways that are activated in response to oxidant injury and those involved in responding to proliferative stimuli, we investigated the role of PLC-␥1 during the cellular response to oxidative stress.

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1,25 dihydroxyvitamin D3 stimulates phospholipase C-gamma in rat colonocytes: role of c-Src in PLC-gamma activation.

Cited by 68 publications

References 41 publications

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

Angiotensin II-induced Association of Phospholipase Cγ1 with the G-protein-coupled AT1 Receptor

The human papillomavirus type 16 E5 protein modulates phospholipase C-γ-1 activity and phosphatidyl inositol turnover in mouse fibroblasts

Oxidative Stress-induced Phospholipase C-γ1 Activation Enhances Cell Survival

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