Gene interactions and pathways from curated databases and text-mining
PloS one 2009, PMID: 19262695

c-Src regulates Akt signaling in response to ghrelin via beta-arrestin signaling-independent and -dependent mechanisms.

Lodeiro, Maria; Theodoropoulou, Marily; Pardo, Maria; Casanueva, Felipe F; CamiƱa, Jesus P

The aim of the present study was to identify the signaling mechanisms to ghrelin-stimulated activation of the serine/threonine kinase Akt. In human embryonic kidney 293 (HEK293) cells transfected with GHS-R1a, ghrelin leads to the activation of Akt through the interplay of distinct signaling mechanisms: an early G(i/o) protein-dependent pathway and a late pathway mediated by beta-arrestins. The starting point is the G(i/o)-protein dependent PI3K activation that leads to the membrane recruitment of Akt, which is phosphorylated at Y by c-Src with the subsequent phosphorylation at A-loop (T308) and HM (S473) by PDK1 and mTORC2, respectively. Once the receptor is activated, a second signaling pathway is mediated by beta-arrestins 1 and 2, involving the recruitment of at least beta-arrestins, c-Src and Akt. This beta-arrestin-scaffolded complex leads to full activation of Akt through PDK1 and mTORC2, which are not associated to the complex. In agreement with these results, assays performed in 3T3-L1 preadipocyte cells indicate that beta-arrestins and c-Src are implicated in the activation of Akt in response to ghrelin through the GHS-R1a. In summary this work reveals that c-Src is crucially involved in the ghrelin-mediated Akt activation. Furthermore, the results support the view that beta-arrestins act as both scaffolding proteins and signal transducers on Akt activation.

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Text Mining Data

Akt → c-Src: " c-Src regulates Akt signaling in response to ghrelin via beta-arrestin signaling independent and -dependent mechanisms "

Akt → mTORC2: " This beta-arrestin scaffolded complex leads to full activation of Akt through PDK1 and mTORC2 , which are not associated to the complex "

Akt → PDK1: " This beta-arrestin scaffolded complex leads to full activation of Akt through PDK1 and mTORC2, which are not associated to the complex "

Akt → c-Src: " In summary this work reveals that c-Src is crucially involved in the ghrelin mediated Akt activation "

Manually curated Databases

  • IRef Biogrid Interaction: AKT1 — ARRB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1 — ARRB2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: AKT1 — CSK (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CSK — ARRB2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CSK — ARRB1 (physical association, affinity chromatography technology)
In total, 5 gene pairs are associated to this article in curated databases