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. 2018 Jul 24;9:910. doi: 10.3389/fphys.2018.00910

FIGURE 3.

FIGURE 3

Release of eIF4E and expression of IGBP1/alpha4 are effectors of mTOR activation. (A) Epo induces weak PI3K/mTOR signaling which causes only partial phosphorylation of 4EBP and fails to release eIF4E. The protein phosphatase PP2A dephosphorylates 4EBP and thereby inhibits eIF4E. In absence of eIF4E, 43 kD complex (see legend Figure 2) cannot associate with mRNA. As a result, erythroid progenitors differentiate (hemoglobin is stained brown in cytospin). (B) Epo plus SCF induces full phosphorylation of 4EBP and release ofeIF4E, which enables asembly of the preinitiation scanning complex at the mRNA cap, and translation of IGBP1 mRNA to produce IGBP1 also known as the alpha4 inhibitory subunit of PP2A. (C) Overexpression of eIF4E out-titrates 4EBP and enables translation of IGBP1 in absence of mTOR activation. (D) Constitutive expression of IGBP1/Alpha4 inhibits dephosphorylation of 4EBP and enables weak PI3K/mTOR activation to result in full phosphorylation of 4EBP, release of eIF4E and translation of IGBP1/Alpha4. (B–D) IGBP1 is an example representing many other transcripts with highly structured 5′UTRs. Cytospins indicate that translation of IGBP1 is associated with proliferation of erythroid progenitors in absence of differentiation.