When comparing initiation in eukaryotes to prokaryotes, perhaps one of the first noticeable differences is the use of a larger 80S ribosome. Regulation of this process begins with the supply of methionine by a tRNA anticodon that basepairs AUG. This base pairing comes about by the scanning mechanism that ensues once the small 40S ribosomal subunit binds the 5 untranslated region (UTR) of mRNA. The usage of this scanning mechanism, in opposition to the Shine-Dalgarno sequence that was referenced in prokaryotes, is the ability to regulate translation through upstream RNA secondary structures. This inhibition of initiation through complex RNA structures may be circumvented in some cases by way of internal ribosomal entry sites (IRESs) that localize pre-initiation complexes (PIC) to the start site. In addition to this, the guidance of the PIC to the 5 UTR is coordinated by subunits of the PIC, known as eukaryotic initiation factors (eIFs). When some of these proteins are down-regulated through stresses, translation initiation is reduced by inhibiting cap dependent initiation, the activation of translation by binding eIF4E to the 5' 7-methylguanylate cap. eIF2 is responsible for coordinating the interaction between the Met-tRNA and the P-site of the ribosome. Regulation by phosphorylation of eIF2 is largely associated with the termination of translation initiation. Serine kinases, GCN2, PERK, PKR, and HRI are examples of detection mechanisms for differing cellular stresses that respond by slowing translation through eIF2 phosphorylation.