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Astrocytes maintained in a chemically defined media undergo differentiation and a parallel increase in pyruvate kinase specific activity. These changes are accompanied by a shift in the isoelectrofocusing pattern, but not by expression of pyruvate kinase M4, the characteristic adult rat brain isozyme. Thus, this chemically defined media lacks a substance required to induce pyruvate kinase M synthesis and this function can be uncoupled from other aspects of cellular differentiation. The uncoupling of pyruvate kinase maturation from cellular differentiation and the observation of only a single, 2.3 kilobase, pyruvate kinase mRNA molecule at different stages of the postnatal development of rat brain support the concept that the K- to M-isoform transformation is a post-transcriptional event. The effect of the individual components of this chemically defined medium on pyruvate kinase specific activity was studied by eliminating one component at a time. The increase in activity was found to be completely dependent upon fibroblastic growth factor and prostaglandin F2 alpha and was partially dependent on the simultaneous presence of insulin.

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P-815 mastocytoma cells increase the level of pyruvate kinase (PK) expression in response to chloroform-methanol extracts of conditioned media, butyrate, and dibutyryl cyclic AMP (but2cAMP) plus theophylline. The butyrate effect is indomethacin sensitive, suggesting a prostaglandin (PG) is the active signaling factor. Moreover, the chloroform-methanol extracts contain PGE2 and PGF2 alpha and additions of the latter enhance PK activity. PGE2 alone has little or no effect but acts synergistically with PGF2 alpha. These data show that PGF2 alpha can regulate PK levels. On the other hand, other factors may also be active, since the endogeneous and the but2cAMP plus theophylline effects are indomethacin insensitive. Most of the factors that increase PK activity also inhibit cellular growth; however, regulation of PK expression can be uncoupled from growth inhibition.