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 rotei n (k) under bar inase C-associated <(kunder bar>inase), was cloned on the b asis 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<(<delta>)under bar>-(i) under bar nteracting (k) under bar inase, DIK (Bahr, C., Rohwer, A., Stempka, L., Rincke, G., M arks, F., and Gschwendlt, M. (2000) J. Biol, Chem. 275, 36350-36357). PKK c omprises an N-terminal kinase domain and a C-terminal region containing 11 ankyrin repeats. PKK exhibits protein kinase activity in vitro and associat es with cellular membranes. PKK exists in three discernible forms at steady state: an underphosphorylated form of 100 kDa; a soluble, cytosolic, phosp horylated form of 110 kDa; and a phosphorylated, detergent-insoluble form o f 112 kDa, PKK is initially synthesized as an underphosphorylated soluble 1 00-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 is oform, However, PKK itself mag be phosphorylated by PKC beta, PKK represent s a developmentally regulated protein kinase that can associate with membra nes. The functional significance of its association with PKC beta remains t o be ascertained.