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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Golgi complex;Erythroleukemia cell;Protein kinase C θ phosphorylation;Thr538→Ala protein kinase Cθ;Thr538→Glu protein kinase Cθ;PKC;protein kinase C;MEL;murine erythroleukaemia;PMA;phorbol myristate acetate;MBP;myelin basic protein;WGA;wheat germ agglutinin;PP;PKCθ pseudosubstrate peptide