A novel transmembrane Ser/Thr kinase complexes with protein phosphatase-1 and inhibitor-2.

Protein kinases and protein phosphatases exert coordinated control over many essential cellular processes. Here, we describe the cloning and characterization of a novel human transmembrane protein KPI-2 (Kinase/Phosphatase/Inhibitor-2) that was identified by yeast two-hybrid using protein phosphatase inhibitor-2 (Inh2) as bait. KPI-2 mRNA was predominantly expressed in skeletal muscle. KPI-2 ...
is a 1503-residue protein with two predicted transmembrane helices at the N terminus, a kinase domain, followed by a C-terminal domain. The transmembrane helices were sufficient for targeting proteins to the membrane. KPI-2 kinase domain has about 60% identity with its closest relative, a tyrosine kinase. However, it only exhibited serine/threonine kinase activity in autophosphorylation reactions or with added substrates. KPI-2 kinase domain phosphorylated protein phosphatase-1 (PP1C) at Thr(320), which attenuated PP1C activity. KPI-2 C-terminal domain directly associated with PP1C, and this required a VTF motif. Inh2 associated with KPI-2 C-terminal domain with and without PP1C. Thus, KPI-2 is a kinase with sites to associate with PP1C and Inh2 to form a regulatory complex that is localized to membranes.
Mesh Terms:
Amino Acid Motifs, Animals, Blotting, Northern, Blotting, Western, COS Cells, Cell Line, Cell Membrane, Cloning, Molecular, DNA, Complementary, Dose-Response Relationship, Drug, Glutathione Transferase, Hela Cells, Humans, Membrane Proteins, Models, Biological, Molecular Sequence Data, Muscle, Skeletal, Phosphoprotein Phosphatases, Phosphorylation, Protein Binding, Protein Phosphatase 1, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Proteins, RNA, Messenger, Rabbits, Recombinant Proteins, Threonine, Tissue Distribution, Transfection, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Dec. 20, 2002
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