3-Phosphoglycerate-dependent protein phosphorylation.

The importance of protein phosphorylation in biological regulation is widely recognized; thus, a number of extracellular signal- and second messenger-linked protein kinases have been well characterized, and various substrates for these kinases have been identified. We present evidence that the glycolytic intermediate 3-phosphoglycerate can cause a marked stimulation of phosphorylation of specific proteins in mammalian tissues. In the brain, there are at least two types of 3-phosphoglycerate-dependent protein phosphorylation systems, which differ in activator specificity, substrate specificity, and sensitivity to the activator. Both of these phosphorylation systems are, however, insensitive to cAMP, cGMP, Ca2+, calmodulin, and protein kinase C activators and have characteristics different from those of casein kinase II-catalyzed protein phosphorylation. The most prominent endogenous substrates in the bovine brain are rather minor proteins with minimal molecular masses of 72 and 155 kDa, which were not detected in "nonnervous" tissues such as heart, liver, lung, and kidney. In nonnervous tissues, 3-phosphoglycerate affected the state of phosphorylation of other proteins. Evidence provided suggests the occurrence of an as yet undescribed type of protein kinase, which may be designated 3-phosphoglycerate-dependent protein kinase, in mammalian tissues.