Sulfur normally exists as an eight-atom molecule, S8, while phosphorus exists as a four-atom molecule, P4

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#Unit 4. Cell Communication and Cell Signaling

PH domain of PKB binds with high affinity to the 

3-phosphates in both PI(3,4)P2 and PI(3,4,5)P3

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#Unit 4. Cell Communication and Cell Signaling

In unstimulated cells, 

concentration of phosphoinositides is low, and PKB is

inactive because its PH domain physically blocks the kinase active site

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#Unit 4. Cell Communication and Cell Signaling

Ligand-induced receptor activation,

Concentration of PI 3-phosphates rises

PH domain of PKB binds to PI 3-phosphates

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#Unit 4. Cell Communication and Cell Signaling

Maximal activation of PKB depends on recruitment to the cytosolic surface of the plasma membrane of two other kinases -PDK1 and PDK2.

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#Unit 4. Cell Communication and Cell Signaling

PDK1 can phosphorylate PKB on a critical threonine residue in its activation loop

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#Unit 4. Cell Communication and Cell Signaling

Phosphorylation by the mTORC2 kinase complex, of a second serine on

PKB that is not in the activation loop is necessary for maximal PKB activity