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mTORC2 regulates the chemoattractant-mediated activation of adenylyl cyclase 9 in a PKC-dependent fashion

Tuesday, October 25, 2011 — Poster Session II

Noon – 2:00 p.m.

Natcher Conference Center




  • LL Liu
  • CA Parent


Chemotaxis is a process by which cells orient themselves and move up a chemical gradient through the directional regulation of actin assembly and actomyosin contractility, which ultimately control front protrusions and back retractions. We previously demonstrated that in neutrophils mTORC2 is required for the chemoattractant-mediated activation of the adenylyl cyclase 9 (AC9), which converts ATP into cAMP, and regulates back contraction through MyoII phosphorylation. Here we studied the mechanism by which mTORC2 regulates AC9 activity. We show that inhibition of conventional PKC but not Akt, two major downstream effectors of mTORC2, severely inhibits chemoattractant-induced cAMP synthesis in neutrophils. Moreover, the specific knock down the PKC isoform betaII by lentiviral shRNA dramatically decreases chemoattractant-induced cAMP production and inhibition of conventional PKC by GO6976 or knock down of PKCbetaII markedly inhibits neutrophil chemotaxis. Remarkably, PKC inhibited cells exhibit specific and severe tail retraction defects. This work reveals that PKCbetaII is required for mTORC2-dependent AC9 activation and back retraction during neutrophil chemotaxis.

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