The Role of Translation Initiation Regulation in Haematopoiesis

Figure 1

The PI3K/PKB/mTOR pathway controls mRNA translation. SCF-receptor activation results in recruitment of PI3K to the receptor, which generates phosphorylates membrane lipids (PIP3) that form an anchor for the PH-domain containing kinases PDK1 and PKB. PIP3 is dephosphorylated by the tumour suppressor PTEN, which silences the PI3K-pathway. At the membrane PDK1 phosphorylates PKB, which phosphorylates the tuberous sclerosis tumour suppressor genes Tsc1 and Tsc2. Upon phosphorylation these genes release the GTPase Rheb to activate mTOR. Activation of mTOR results in phosphorylation of p70S6kinase (S6K) and eIF4E-binding protein (4E-BP). Upon phosphorylation, 4E-BP releases the cap-binding translation initiation factor 4E (eIF4E), which allows for association of eIF4E with the proteins that form the eIF4F scanning complex and with the 40S ribosomal subunit [4].