Protein kinase C-associated kinase (PKK), a novel membrane-associated, ankyrin repeat-containing protein kinase

A novel murine membrane-associated protein kinase, PKK ((p) under bar rotein (k) under bar inase C-associated <(kunder bar>inase), was cloned on the basis of its physical association with protein kinase C beta (PKC beta), The regulated expression of PKK in mouse embryos is consistent with a role for this kinase in early embryogenesis, The human homolog of PKK has over 90% identity to its murine counterpart, has been localized to chromosome 21q22,3, and is identical to the PKC<()under bar>-(i) under bar nteracting (k) under bar inase, DIK (Bahr, C., Rohwer, A., Stempka, L., Rincke, G., Marks, F., and Gschwendlt, M. (2000) J. Biol, Chem. 275, 36350-36357). PKK comprises an N-terminal kinase domain and a C-terminal region containing 11 ankyrin repeats. PKK exhibits protein kinase activity in vitro and associates with cellular membranes. PKK exists in three discernible forms at steady state: an underphosphorylated form of 100 kDa; a soluble, cytosolic, phosphorylated form of 110 kDa; and a phosphorylated, detergent-insoluble form of 112 kDa, PKK is initially synthesized as an underphosphorylated soluble 100-kDa protein that is quantitatively converted to a detergent-soluble 110-kDa form. This conversion requires an active catalytic domain. Although PKK physically associates with PKC beta, it does not phosphorylate this PKC isoform, However, PKK itself mag be phosphorylated by PKC beta, PKK represents a developmentally regulated protein kinase that can associate with membranes. The functional significance of its association with PKC beta remains to be ascertained.