Additional information

AKT1 module AKT1 module encompasses components and reaction involved in activation of AKT1-mTOR cascade downstream of the CCKR (Table 1). Both gastrin and CCK activate PI3K via SRC dependent mechanism [1, 2]. Our model shows that gastrin activates tyrosine phosphorylation of IRS1 and its association with p85 subunit of PI3K by recruiting p85/p110 complex at the plasma membrane [3, 4]. Association of IRS1 with p85 activates PI3K complex. CCK2R stimulated JAK2 is documented to function upstream of PI3K in regulation of cell adhesion [5]. Active PI3K triggers PI3K dependent cascade by catalyzing PIP2 into PIP3. Activation of PI3K cascade promotes the recruitment of proteins with pleckstrin homology (PH) domains such as AKT1 and PDPK1 to the plasma membrane. Upon binding to the membrane, AKT1 and PDPK1 become active. Notably, translocation of AKT1 to the plasma membrane also facilitates its phosphorylation by PDPK1 [6, 7]. This cascade of events phosphorylates AKT1 at Ser308 and Ser473 to make it active. It is likely, that activated AKT1 regulates mTOR pathway and stimulates activation of Ribosomal protein S6 kinases 70kDa (p70 S6 kinase) because mTORC1 and PI3K specific inhibitor rapamycin, inhibits gastrin dependent p70S6K activity [8].