Role of the kinase activation loop on protein kinase C θ activity and intracellular localisation

Abstract

Multiple protein kinase C (PKC) θ species, identified in an erythroleukaemia cell line, have been characterised in terms of their molecular properties and intracellular distribution. PKCθs localised in the detergent‐soluble cell fraction have an M _r of 76 kDa (θ‐76) and contain Thr⁵³⁸ or pThr⁵³⁸ in the kinase activation loop. In contrast, PKCθs localised in the Golgi complex have an M _r of 85 kDa (θ‐85) and, although unphosphorylated at Thr⁵³⁸, are catalytically active. Strikingly, only θ‐76 species which are unphosphorylated at Thr⁵³⁸ can undergo autocatalytic conversion to θ‐85. Moreover, a Thr⁵³⁸→Ala PKCθ mutant is constitutively localised in the Golgi complex, confirming that changes in the phosphorylation state of this residue play a pivotal role in the overall control of catalytic properties and localisation of this kinase.