A novel regulatory mechanism links PLCγ1 to PDK1

Claudio Raimondi, Anissa Chikh, Ann P Wheeler, Tania Maffucci, Marco Falasca

Research output: Contribution to journalArticlepeer-review

Abstract

3-Phosphoinositide-dependent protein kinase-1 (PDK1) and phospholipase C (PLC)γ1 are two key enzymes in signal transduction that control several intracellular processes. Despite the fact that PLCγ1 has been investigated for several years, the mechanisms of activation of this enzyme are still not completely clear. Similarly, although PDK1 has been mostly investigated for its role in activation of Akt, a crucial enzyme in regulation of several cellular processes, it has become evident recently that the role of PDK1 in physiological and pathological conditions is not limited to Akt activation. Here we demonstrate that PDK1 regulates PLCγ1 activation in a mechanism involving association of the two enzymes and modulation of PLCγ1 tyrosine phosphorylation. We further show that this novel PDK1-PLCγ1 pathway is important for cancer cell invasion. The identification of a PDK1-PLCγ1 pathway reveals the existence of a previously undetected link between two of the most important enzymes in signal transduction. This is likely to have profound consequences for our understanding of several cellular functions that are dependent on phosphoinositides and controlled by PDK1 and PLCγ1.

Original languageEnglish
Pages (from-to)3153-63
Number of pages11
JournalJournal of Cell Science
Volume125
Issue numberPt 13
DOIs
Publication statusPublished - 1 Jul 2012

Keywords

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Calcium
  • Enzyme Activation
  • Epidermal Growth Factor
  • Flow Cytometry
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • Indazoles
  • Neoplasm Invasiveness
  • Phospholipase C gamma
  • Phosphorylation
  • Protein Interaction Mapping
  • Protein-Serine-Threonine Kinases
  • Pyrimidines
  • RNA, Small Interfering
  • Receptor, Epidermal Growth Factor
  • Signal Transduction
  • Transfection

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