AUTOPHOSPHORYLATION-ACTIVATED PROTEIN-KINASE INACTIVATES THE PROTEIN-TYROSINE-PHOSPHATASE ACTIVITY OF PROTEIN PHOSPHATASE 2A

Phosphorylation of the catalytic subunit of protein phosphatase 2A (PP 2A) on threonines with a distinct autophosphorylation-activated protei n kinase [Guo and Damuni (1993) Proc, Natl. Acad. Sci. USA 90, 2500-25 04] inactivated the phosphatase with P-32-labelled myelin basic protei n prepared by incubation with the kinase domain of the epidermal growt h factor receptor, the src-family protein kinases p56(lck) and p60(c-s rc), myelin basic protein kinase-1, or protamine kinase. Phosphoamino acid analysis demonstrated that the kinase domain of the epidermal gro wth factor receptor, p56(lck) and p60(c-src) phosphorylated myelin bas ic protein on tyrosines, that the protamine kinase phosphorylated myel in basic protein on serines, and that myelin basic protein kinase-1 ph osphorylated myelin basic protein on threonines. The results demonstra te that the autophosphorylation-activated protein kinase not only inac tivates the protein serine/threonine phosphatase, but also the protein tyrosine phosphatase activity of PP2A. This autophosphorylation-activ ated protein kinase-mediated inactivation of PP2A may, in response to extracellular stimuli, not only contribute to the enhanced phosphoryla tion of cellular proteins on serines and threonines but also on tyrosi nes.