On the role of the cAMP and cGMP-dependent protein kinases in cell function.

Cyclic AMP and cGMP-dependent protein kinases have many similarities in physical and kinetic properties. Thus, the two enzymes appear to be homologous proteins, even though the subunit compositions of the two enzymes differ. Of several possible evolutionary schemes, two likely ones are proposed: (i) the ancestral protein kinase was composed of a single type of subunit which evolved into separate regulatory and catalytic subunits by gene splitting; or (ii) the ancestral protein kinase was composed of separate regulatory and catalytic subunits which evolved into a single type of subunit by gene fusion. The evolutionary parallelism poses interesting questions on the functional relatwonships between the two enzymes. Although, there is overlapping substrate specificity between the two kinases, the cAMP kinase is generally a more efficient and versatile catalyst than the cGMP kinase. This difference in catalytic versatility could have offered an evolutionary advantage to the cAMP kinase, and could explain the more widespread distribution of this enzyme in mammalian tissues. The cGMP kinase is proposed to be a more specific enzyme than the cAMP kinase. This implies a less diverse role for cGMP in the regulation of cell function.