Phosphoprotein-Specific Antibodies

Forty-six years ago, Edwin Krebs and colleagues changed the way researchers understood the regulation of protein activity. In a landmark paper, these authors described the regulation of glycogen phosphorylase by attachment of a phosphate group.¹ Four years later, these same authors discovered that this phosphorylation event was mediated by the enzyme glycogen phosphorylase kinase (kinases are enzymes that catalyze the transfer of a phosphate group from ATP to a substrate protein).² And nine years after that, they demonstrated that glycogen phosphorylase kinase was itself regulated by glycogen phosphorylase kinase kinase (now referred to as cAMP-dependent protein kinase, cAPK).³

Other researchers partially explained the relationship of the cascading control of these enzymes with the second messenger concept, proposed in 1955.⁴ The second messenger hypothesis explains how an extracellular signal (such as hormone binding to a receptor) can be translated into a rapid, strong, intracellular response. The activation...