Modulation of GSK‐3‐catalyzed phosphorylation of microtubule‐associated protein tau by non‐proline‐dependent protein kinases

Abstract

The phosphorylation of bovine tau, either by GSK‐3 alone or by a combination of GSK‐3 and several non‐proline‐dependent protein kinases (non‐PDPKs), was studied. GSK‐3 alone catalyzed the incorporation of ∼ 3 mol ³²P/mot tau at a relatively slow rate. Prephosphorylation of tau by A‐kinase, C‐kinase, or CK‐2 (but not by CK‐1, CaM kinase II or Gr kinase) increased both the rate and extent of a subsequent phosphorylation catalyzed by GSK‐3 by several‐fold. These results suggest that the phosphorylation of tau by PDPKs such as GSK‐3 (and possibly MAP kinase, cdk5) may be positively modulated at the substrate level by non‐PDPK‐catalyzed phosphorylations.