Association of Heterotrimeric G-Proteins with Bovine Aortic Phospholipase C γ

Hodson, Elizabeth A.M.; Ashley, Christopher; Lymn, Joanne

doi:10.1006/bbrc.1999.0657

Cited by 2 publications

(1 citation statement)

References 47 publications

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“…Cell proliferation and wound recovery were also attenuated suggesting that the association of G␤ with PLC␥1 has an important role in o-HA-induced cell signaling. Other studies have described an association between PLC␥1 and G␣ i proteins in BAEC resulting in PLC␥1 activation (61). This association usually occurred in the presence of another tyrosine kinaseactivated co-precipitant such as Src kinase.…”

Section: Discussionmentioning

confidence: 96%

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Slevin

Kumar

Gaffney

2002

Journal of Biological Chemistry

314

228

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Hyaluronan (HA) is a large nonsulfated glycosaminoglycan and an important regulator of angiogenesis, in particular, the growth and migration of vascular endothelial cells. We have identified some of the key intermediates responsible for induction of mitogenesis and wound recovery. Treatment of bovine aortic endothelial cells with oligosaccharides of hyaluronan (o-HA) resulted in rapid tyrosine phosphorylation and plasma membrane translocation of phospholipase C␥1 (PLC␥1). Cytoplasmic loading with inhibitory antibodies to PLC␥1, G␤, and G␣ i/o/t/z inhibited activation of extracellular-regulated kinase 1/2 (ERK1/2). Treatment with the G␣ i/o inhibitor, pertussis toxin, reduced o-HA-induced PLC␥1 tyrosine phosphorylation, protein kinase C (PKC) ␣ and ␤1/2 membrane translocation, ERK1/2 activation, mitogenesis, and wound recovery, suggesting a mechanism for o-HA-induced angiogenesis through Gproteins, PLC␥1, and PKC. In particular, we demonstrated a possible role for PKC␣ in mitogenesis and PKC␤1/2 in wound recovery. Using antisense oligonucleotides and the Ras farnesylation inhibitor FTI-277, we showed that o-HA-induced bovine aortic endothelial cell proliferation, wound recovery, and ERK1/2 activation were also partially dependent on Ras activation, and that o-HA-stimulated tyrosine phosphorylation of the adapter protein Shc, as well as its association with Sos1. Binding of Src to Shc was required for its activation and for Ras-dependent activation of ERK1/2, cell proliferation, and wound recovery. Neither Src nor Ras activation was inhibited by pertussis toxin, suggesting that their activation was independent of heterotrimeric G-proteins. However, the specific Src kinase inhibitor PP2 inhibited G␤ subunit co-precipitation with PLC␥1, suggesting a possible role for Src in activation of PLC␥1 and interaction between two distinct o-HA-induced signaling pathways.

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Section: Discussionmentioning

confidence: 96%

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Slevin

Kumar

Gaffney

2002

Journal of Biological Chemistry

314

228

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Linking phospholipase C isoforms with differentiation function in human vascular smooth muscle cells

Mackenzie

Lymn

Hughes

2013

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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The phosphoinositol-phospholipase C (PLC) family of enzymes consists of a number of isoforms, each of which has different cellular functions. PLCγ1 is primarily linked to tyrosine kinase transduction pathways, whereas PLCδ1 has been associated with a number of regulatory proteins, including those controlling the cell cycle. Recent studies have shown a central role of PLC in cell organisation and in regulating a wide array of cellular responses. It is of importance to define the precise role of each isoform, and how this changes the functional outcome of the cell. Here we investigated differences in PLC isoform levels and activity in relation to differentiation of human and rat vascular smooth muscle cells. Using Western blotting and PLC activity assay, we show that PLCδ1 and PLCγ1 are the predominant isoforms in randomly cycling human vascular smooth muscle cells (HVSMCs). Growth arrest of HVSMCs for seven days of serum deprivation was consistently associated with increases in PLCδ1 and SM α-actin, whereas there were no changes in PLCγ1 immuno-reactivity. Organ culture of rat mesenteric arteries in serum free media (SFM), a model of de-differentiation, led to a loss of contractility as well as a loss of contractile proteins (SM α-actin and calponin) and PLCδ1, and no change in PLCγ1 immuno-reactivity. Taken together, these data indicate that PLCδ1 is the predominant PLC isoform in vascular smooth muscle, and confirm that PLCδ1 expression is affected by conditions that affect the cell cycle, differentiation status and contractile function.

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Association of Heterotrimeric G-Proteins with Bovine Aortic Phospholipase C γ

Cited by 2 publications

References 47 publications

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Angiogenic Oligosaccharides of Hyaluronan Induce Multiple Signaling Pathways Affecting Vascular Endothelial Cell Mitogenic and Wound Healing Responses

Linking phospholipase C isoforms with differentiation function in human vascular smooth muscle cells

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