Protein kinase B signaling cascade ; GO:0043491

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PROTEIN KINASE B SIGNALING

PKB = AKT

http://www.cellsignal.com/reference/pathway/Akt_PKB.html

ACTIVATION OF PKB

PI3K-DEPENDENT PKB/AKT ACTIVATION

  • PKB/AKT binds the phosphoinositides PIP2 and PIP3 (generated by PI3K), localizing PKB to the cell membrane.
  • Following localization to the membrane, PKB is phosphorylated by its activating kinases (first on Serine by PDK2/mTORC2, and then on Threonine by PDK1)


PI3K-INDEPENDENT PKB/AKT ACTIVATION

  • Tyr phosphorylation by ACK1 (rarer form of activation) (see PMID 20333297)


DOWNSTREAM TARGETS OF PKB

  • lots and lots and lots
  • mTOR
  • Bcl-2 family members (e.g. PKB phosphorylates BAD to inhibit its pro-apoptotic function)
  • GSK3 (thereby regulate glucose metabolism)


REGULATION OF PKB SIGNALING

  • PTEN: PI3K-dep PKB activation is INHIBITED by PTEN, which counteracts the activity of PI3K (dephosphorylates PIP3 to PIP2)
  • SHIP Phosphatases: SHIP phosphatases can directly dephosphorylate AKT to inactivate it.


QUESTIONS

Another intracellular signaling pathway that named after one mediator.

  • What is included in PI3K signaling?.... everything ABOVE and BELOW PI3K? Or does PI3K signaling begin WITH the activity of PI3K.


REFERENCES

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