Figure 8
Schematic of proposed mechanism by which EGF stimulation leads to increased LDLR expression. (1) EGF stimulation of the EGF receptor leads to dimerization and phosphorylation of the EGFR. (2) Phosphorylation of the EGFR leads to activation of the MAPK signaling pathway (two arrows indicate intermediaries not shown in the schematic between the EGFR and p44/42 MAPK). Phosphorylation of MAPK leads to activation of p90RSK. (3) ZFP36L1 binds to AU-rich regions within the 3′ untranslated region of LDLR mRNA and associates with the deadenylation complex subunit, CNOT7 (not shown in schematic)20 leading to RNA degradation. (4) Phosphorylation of ZFP36L1 prevents RNA degradation therefore increasing LDLR mRNA levels. (5) LDLR mRNA is translated by the membrane bound ribosomes of the rough endoplasmic reticulum and fully glycosylated in the Golgi. (6) The LDLRs are then transported in vesicles to the cell membrane where they are found in clathrin-coated pits. (7) LDL binds to the LDLR on the cell surface leading to internalization of the LDL/LDLR complex.
