ROLES OF SEVERAL DOMAINS IDENTIFIED IN THE PRIMARY STRUCTURE OF SALT-INDUCIBLE KINASE (SIK)

Abstract

Salt-inducible kinase (SIK), a 776 amino acids-protein, contains a kinase domain in the NH₂-terminal 278 amino acid residues, and the biological functions of its COOH-terminal half have yet to be clarified. Here we describe the roles played by several domains in the SIK molecule. K⁵⁶, an amino acid residue found in a region similar to the ATP-binding loop of other protein kinases, was essential for carrying out the SIKs phosphorylation reaction. An SNF-1 homology domain (SNH), identified at a peptide stretch from the 317th to the 346th residues, and conserved among all the sucrose-nonfermenting-1 protein kinase (SNF-1) family protein kinases, was important to maintain the SIKs protein conformation in the cells. S⁵⁷⁷, an amino acid residue found in one of three consensus PKA-dependent phosphorylation motifs, was indeed phosphorylated by PKA. The phosphorylated SIK was found to move out of the nucleus to the cytoplasm.