Control of polypeptide synthesis plays an important role in cell proli
feration and translation rates generally reflect the growth state of t
he cultured eukaryotic cell. Physiological regulation of protein synth
esis is almost always exerted at the level of polypeptide chain initia
tion, with the binding of mRNA to the small ribosomal subunit a rate-l
imiting step in many cell systems. Studies have indicated key roles in
the regulation of protein synthesis for the structural features of mR
NA molecules and phosphorylation of initiation factors which catalyse
this process. This review focusses on translational regulation at the
level of mRNA binding to the ribosome and the role of phosphorylation
of initiation factors in mediating both quantitative and qualitative c
ontrol. The identity of putative kinases which may mediate these proce
sses is addressed and a possible model for the role of a transient act
ivation of initiation factors in cell growth or differentiation is pre
sented.