U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream of phospholipase C in CHO cells

Bosch, Remko R.; Patel, Anjana; Vries, S. E. Van Ernst-De; Smeets, R.L.L.; Pont, J.J.H.H.M. de; Willems, Peter H.G.M.

doi:10.1016/s0014-2999(98)00070-3

Cited by 31 publications

(23 citation statements)

References 17 publications

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“…4B), suggesting a contribution of PKC to clustering and subsequent stable adhesion. The effect of PKC inhibition on ALCAM-mediated adhesion was not due to a direct effect of CytD or LatA on PKC, since PKC activity, as determined by Bosch et al (Bosch et al, 1998), was not altered in the presence of CytD or LatA (data not shown). Activation of PKC by the addition of PMA (50 nM) did not induce adhesion (data not shown), indicating that PKC alone is not sufficient to overcome the cytoskeletal restraints, but that disruption of the actin cytoskeleton has to coincide with PKC action.…”

Section: Fig 3 (A) Expression Of Myc-tagged Rho-like Gtpase-mutantsmentioning

confidence: 63%

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Zimmerman

Nelissen

Vries³

et al. 2004

Journal of Cell Science

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The activated leukocyte cell adhesion molecule (ALCAM) is dynamically regulated by the actin cytoskeleton. In this study we explored the molecular mechanisms and signaling pathways underlying the cytoskeletal restraints of this homotypic adhesion molecule. We observed that ALCAM-mediated adhesion induced by cytoskeleton-disrupting agents is accompanied by activation of the small GTPases RhoA, Rac1 and Cdc42. Interestingly, unlike adhesion mediated by integrins or cadherins, ALCAM-mediated adhesion appears to be independent of Rho-like GTPase activity. By contrast, we demonstrated that protein kinase C (PKC) plays a major role in ALCAM-mediated adhesion. PKC inhibition by chelerythrine chloride and myristoylated PKC pseudosubstrate, as well as PKC downregulation by PMA strongly reduce cytoskeleton-dependent ALCAM-mediated adhesion. Since serine and threonine residues are dispensable for ALCAM-mediated adhesion and ALCAM is not phosphorylated, we can rule out that ALCAM itself is a direct PKC substrate. We conclude that PKCα plays a dominant role in cytoskeleton-dependent avidity modulation of ALCAM.

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Section: Fig 3 (A) Expression Of Myc-tagged Rho-like Gtpase-mutantsmentioning

confidence: 63%

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Zimmerman

Nelissen

Vries³

et al. 2004

Journal of Cell Science

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“…35 Inasmuch as U73122 also inhibits phospholipase D, 27 it is possible that coincident signaling via RhoA and/or phospholipase D mediates in part the interaction between the G i pathway and Ang II and AVP.…”

Section: Discussionmentioning

confidence: 99%

“…Some animals received 3 concomitant intrarenal infusions. In these animals, the third intrarenal infusion was U73122, a widely used phospholipase C inhibitor 26 that also inhibits phospholipase D. 27 U73122 was infused at 5 L/min and was dissolved in dimethyl sulfoxide. After surgery, animals were given a bolus injection of captopril (30 mg/kg) to remove the influence of endogenous Ang II and a bolus of 0.9% saline (20 mL/kg) to improve hemodynamic stability.…”

Section: Surgical Preparationmentioning

confidence: 99%

Enhanced Interaction Between Renovascular α ₂ -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

et al. 2001

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“…However, it either has no effect on purified PLC enzymes or stimulates PLC activity in vitro at somewhat higher concentrations (ϳ10 M) (802). U73122 also inhibits a number of Ca 2ϩ -regulated processes independent of its putative effects on PLC (169,1240,1660,1817). The fact that its nonreactive control compound U-73343 does not reproduce the effects of the active compound, by no means is a satisfying criterion to indicate specificity on PLC.…”

Section: Phospholipase C Enzymesmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,357

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream of phospholipase C in CHO cells

Cited by 31 publications

References 17 publications

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Enhanced Interaction Between Renovascular α ₂ -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

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U73122 and U73343 inhibit receptor-mediated phospholipase D activation downstream of phospholipase C in CHO cells

Cited by 31 publications

References 17 publications

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Enhanced Interaction Between Renovascular α 2 -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

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Enhanced Interaction Between Renovascular α ₂ -Adrenoceptors and Angiotensin II Receptors in Genetic Hypertension