RGD Reference Report - ANG II stimulates phospholipase D through PKCzeta activation in VSMC: implications in adhesion, spreading, and hypertrophy. - Rat Genome Database

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ANG II stimulates phospholipase D through PKCzeta activation in VSMC: implications in adhesion, spreading, and hypertrophy.

Authors: Parmentier, JH  Pavicevic, Z  Malik, KU 
Citation: Parmentier JH, etal., Am J Physiol Heart Circ Physiol. 2006 Jan;290(1):H46-54. Epub 2005 Aug 19.
RGD ID: 1642674
Pubmed: PMID:16113073   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00769.2005   (Journal Full-text)

ANG II stimulates phospholipase D (PLD) activity and growth of vascular smooth muscle cells (VSMC). The atypical protein kinase C-zeta (PKCzeta) plays a central role in the regulation of cell survival and proliferation. This study was conducted to determine the relationship between ANG II-induced activation of PKCzeta and PLD and their implication in VSMC adhesion, spreading, and hypertrophy. ANG II stimulated PKCzeta activity with maximal activation at 30 s followed by a decline in its activity to 45% above basal at 5 min. Inhibition of PKCzeta activity with a myristoylated pseudosubstrate peptide or overexpression of a kinase-inactive form of PKCzeta decreased ANG II-induced PLD activity. Moreover, depletion of PKCzeta with selective antisense oligonucleotides also decreased ANG II-induced PLD activity. Interaction between PLD2 and PKCzeta in VSMC was detected by coimmunoprecipitation. ANG II-induced PLD activity was inhibited by the primary alcohol n-butanol but not the tertiary alcohol t-butanol. The functional significance of PKCzeta and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated. Inhibition of PKCzeta and PLD2 activity or expression attenuated VSMC adhesion to collagen I and ANG II-induced cell spreading and hypertrophy. These results demonstrate that ANG II-induced PLD activation is regulated by PKCzeta and suggest a crucial role of PKCzeta-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
activation of phospholipase D activity  IMP 1642674 RGD 
positive regulation of cell-matrix adhesion  IMP 1642674vascular smooth muscle cell adhesion to collagen matrixRGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phospholipase binding  IPIPld2 (Rattus norvegicus)1642674 RGD 
protein kinase C binding  IPIPrkcz (Rattus norvegicus)1642674 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
angiotensin II signaling pathway   IMP 1642674 RGD 
Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
vascular smooth muscle hypertrophy  IDA 1642674; 1642674angiotensin II inducedRGD 
Objects Annotated

Genes (Rattus norvegicus)
Pld2  (phospholipase D2)
Prkcz  (protein kinase C, zeta)


Additional Information