Two phosphorylation sites on eIF-2 alpha

Protein synthesis in mammalian cells can be regulated through phosphorylation/dephosphorylation of the alpha subunit of initiation factor 2, eIF-2. Two specific kinases have been identified that apparently phosphorylate the same site(s). Controversy exists as to whether serine-48 is a phosphorylation site in addition to serine-51. A recent publication is discussed that, in this author's view, answers the question of the phosphorylation sites. It is suggested that phosphorylation proceeds sequentially with serine-51 being the first and serine-48 the second phosphorylation site. Phosphorylation of both sites is required for inhibition of protein synthesis.