Datta A, de Haro C, Sierra J M, Ochoa S
Proc Natl Acad Sci U S A. 1977 Aug;74(8):3326-9. doi: 10.1073/pnas.74.8.3326.
The formation of translational inhibitor (active eIF-2 kinase) from proinhibitor (inactive eIF-2 kinase) in reticulocyte lysates, known to be controlled by hemin, can, as we recently reported, be induced by 3':5'-cyclic AMP(cAMP)-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) or its catalytic subunit. We find that in crude preparations from rabbit reticulocyte lysates, hemin inhibits the conversion of proinhibitor to inhibitor catalyzed by endogenous cAMP-dependent protein kinase upon addition of cAMP, but not that caused by the addition of free protein kinase catalytic subunit. Hemin prevents the binding of cAMP to the regulatory subunit of cAMP-dependent protein kinase and blocks the cAMP-induced dissociation of regulatory and catalytic subunits of the enzyme whereby the enzyme is inactivated. The mechanism by which hemin prevents the formation of the inhibitor and maintains protein synthesis in reticulocyte lysates is thus explained.
网织红细胞裂解物中由前抑制剂（无活性的eIF-2激酶）形成翻译抑制剂（活性eIF-2激酶）的过程，已知受血红素调控，正如我们最近报道的，可由3':5'-环磷酸腺苷（cAMP）依赖性蛋白激酶（ATP:蛋白磷酸转移酶，EC 2.7.1.37）或其催化亚基诱导。我们发现，在兔网织红细胞裂解物的粗制品中，加入cAMP后，血红素会抑制内源性cAMP依赖性蛋白激酶催化的前抑制剂向抑制剂的转化，但不会抑制加入游离蛋白激酶催化亚基所导致的转化。血红素会阻止cAMP与cAMP依赖性蛋白激酶的调节亚基结合，并阻断cAMP诱导的该酶调节亚基与催化亚基的解离，从而使该酶失活。由此解释了血红素阻止抑制剂形成并维持网织红细胞裂解物中蛋白质合成的机制。
