Src promotes PKCδ degradation

Robert A. Blake, Pilar Garcia-Paramio, Peter J. Parker, Sara Courtneidge

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Platelet-derived growth factor BB (PDGF) stimulates DNA synthesis through a mechanism that is at least partially dependent upon Src family tyrosine kinases, although the signal transduction pathway downstream of Src is poorly understood. We have studied the signaling between Src and different protein kinase C (PKC) isoforms and its possible role in the regulation of PDGF-stimulated DNA synthesis. We found that Src promoted the tyrosine phosphorylation of PKCδ, and its subsequent degradation. Enforced expression of PKCδ inhibited PDGF-stimulated DNA synthesis, whereas expression of PKCα and PKCε did not, a finding consistent with a model in which PKCδ negatively regulates G1-to-S-phase progression. We used mutagenesis to map a critical Src phosphorylation site on PKCδ to tyrosine 311. A mutant form of PKCδ in which tyrosine 311 was replaced with phenylalanine (Y311F) was more stable in the presence of Src, suggesting that Src-induced degradation was a direct result of PKCδ tyrosine phosphorylation. We conclude that PKCδ is downstream of Src but is unlikely to play a positive role in the signaling pathway by which Src promotes DNA synthesis.

Original languageEnglish (US)
Pages (from-to)231-241
Number of pages11
JournalCell Growth and Differentiation
Volume10
Issue number4
StatePublished - Apr 1999
Externally publishedYes

Fingerprint

Protein Kinase C
Tyrosine
DNA
Phosphorylation
src-Family Kinases
Mutant Proteins
Phenylalanine
S Phase
Mutagenesis
Protein-Tyrosine Kinases
Signal Transduction
Protein Isoforms
platelet-derived growth factor BB

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Blake, R. A., Garcia-Paramio, P., Parker, P. J., & Courtneidge, S. (1999). Src promotes PKCδ degradation. Cell Growth and Differentiation, 10(4), 231-241.

Src promotes PKCδ degradation. / Blake, Robert A.; Garcia-Paramio, Pilar; Parker, Peter J.; Courtneidge, Sara.

In: Cell Growth and Differentiation, Vol. 10, No. 4, 04.1999, p. 231-241.

Research output: Contribution to journalArticle

Blake, RA, Garcia-Paramio, P, Parker, PJ & Courtneidge, S 1999, 'Src promotes PKCδ degradation', Cell Growth and Differentiation, vol. 10, no. 4, pp. 231-241.
Blake RA, Garcia-Paramio P, Parker PJ, Courtneidge S. Src promotes PKCδ degradation. Cell Growth and Differentiation. 1999 Apr;10(4):231-241.
Blake, Robert A. ; Garcia-Paramio, Pilar ; Parker, Peter J. ; Courtneidge, Sara. / Src promotes PKCδ degradation. In: Cell Growth and Differentiation. 1999 ; Vol. 10, No. 4. pp. 231-241.
@article{78d3748e9425426ca69e558961875736,
title = "Src promotes PKCδ degradation",
abstract = "Platelet-derived growth factor BB (PDGF) stimulates DNA synthesis through a mechanism that is at least partially dependent upon Src family tyrosine kinases, although the signal transduction pathway downstream of Src is poorly understood. We have studied the signaling between Src and different protein kinase C (PKC) isoforms and its possible role in the regulation of PDGF-stimulated DNA synthesis. We found that Src promoted the tyrosine phosphorylation of PKCδ, and its subsequent degradation. Enforced expression of PKCδ inhibited PDGF-stimulated DNA synthesis, whereas expression of PKCα and PKCε did not, a finding consistent with a model in which PKCδ negatively regulates G1-to-S-phase progression. We used mutagenesis to map a critical Src phosphorylation site on PKCδ to tyrosine 311. A mutant form of PKCδ in which tyrosine 311 was replaced with phenylalanine (Y311F) was more stable in the presence of Src, suggesting that Src-induced degradation was a direct result of PKCδ tyrosine phosphorylation. We conclude that PKCδ is downstream of Src but is unlikely to play a positive role in the signaling pathway by which Src promotes DNA synthesis.",
author = "Blake, {Robert A.} and Pilar Garcia-Paramio and Parker, {Peter J.} and Sara Courtneidge",
year = "1999",
month = "4",
language = "English (US)",
volume = "10",
pages = "231--241",
journal = "Molecular Cancer Research",
issn = "1541-7786",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Src promotes PKCδ degradation

AU - Blake, Robert A.

AU - Garcia-Paramio, Pilar

AU - Parker, Peter J.

AU - Courtneidge, Sara

PY - 1999/4

Y1 - 1999/4

N2 - Platelet-derived growth factor BB (PDGF) stimulates DNA synthesis through a mechanism that is at least partially dependent upon Src family tyrosine kinases, although the signal transduction pathway downstream of Src is poorly understood. We have studied the signaling between Src and different protein kinase C (PKC) isoforms and its possible role in the regulation of PDGF-stimulated DNA synthesis. We found that Src promoted the tyrosine phosphorylation of PKCδ, and its subsequent degradation. Enforced expression of PKCδ inhibited PDGF-stimulated DNA synthesis, whereas expression of PKCα and PKCε did not, a finding consistent with a model in which PKCδ negatively regulates G1-to-S-phase progression. We used mutagenesis to map a critical Src phosphorylation site on PKCδ to tyrosine 311. A mutant form of PKCδ in which tyrosine 311 was replaced with phenylalanine (Y311F) was more stable in the presence of Src, suggesting that Src-induced degradation was a direct result of PKCδ tyrosine phosphorylation. We conclude that PKCδ is downstream of Src but is unlikely to play a positive role in the signaling pathway by which Src promotes DNA synthesis.

AB - Platelet-derived growth factor BB (PDGF) stimulates DNA synthesis through a mechanism that is at least partially dependent upon Src family tyrosine kinases, although the signal transduction pathway downstream of Src is poorly understood. We have studied the signaling between Src and different protein kinase C (PKC) isoforms and its possible role in the regulation of PDGF-stimulated DNA synthesis. We found that Src promoted the tyrosine phosphorylation of PKCδ, and its subsequent degradation. Enforced expression of PKCδ inhibited PDGF-stimulated DNA synthesis, whereas expression of PKCα and PKCε did not, a finding consistent with a model in which PKCδ negatively regulates G1-to-S-phase progression. We used mutagenesis to map a critical Src phosphorylation site on PKCδ to tyrosine 311. A mutant form of PKCδ in which tyrosine 311 was replaced with phenylalanine (Y311F) was more stable in the presence of Src, suggesting that Src-induced degradation was a direct result of PKCδ tyrosine phosphorylation. We conclude that PKCδ is downstream of Src but is unlikely to play a positive role in the signaling pathway by which Src promotes DNA synthesis.

UR - http://www.scopus.com/inward/record.url?scp=0032587890&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032587890&partnerID=8YFLogxK

M3 - Article

VL - 10

SP - 231

EP - 241

JO - Molecular Cancer Research

JF - Molecular Cancer Research

SN - 1541-7786

IS - 4

ER -