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A prenylation motif is required for plasma membrane localization and biochemical function of casein kinase I in budding yeast.

1994; Elsevier BV; Volume: 269; Issue: 30 Linguagem: Inglês

10.1016/s0021-9258(17)32163-4

1083-351X

Aleš Vančura, Anna M. Sessler, Betty N. Leichus, Jeff Kuret,

Endoplasmic Reticulum Stress and Disease

The subcellular distribution of three casein kinase I (CK1) homologs, encoded by the YCKl, YCK2, and HRR25 genes, has been determined in budding yeast through a combination of subcellular fractionation and immunofluorescence methods.Both Yck proteins are tightly associated with the plasma membrane or underlying cytoskeleton and require both high-salt and nonionic detergent for extraction.Association is mediated primarily by the prenylation motif found at the C terminus of both Yck proteins.In contrast, the third CK1 homolog, Hrr25p, is found predominantly in the nucleus and only partially in the plasma membrane.Despite partial colocalization with the Yck proteins, Hrr25p is unable to rescue the ycklAyck2A phenotype.However, a chimeric kinase containing the N-terminal kinase domain of Hrr25p and the C-terminal region of Yck2p contains full Yck activity in vivo.These data suggest that members of the casein kinase I family have distinct but partially overlapping distributions in the cell that are mediated by their unique C-terminal regions.Casein kinase I (CK1)' is a protein kinase common to all eukaryotic cells (1, 2).Once considered a single entity, it is now known to consist of multiple isoforms that together comprise a distinct branch of the eukaryotic protein kinase family (3-8).Family members identified to date consist of a highly conserved N-terminal catalytic domain joined to a variable C-terminal region that is not conserved between family members and that is variable in length.The catalytic domain is characterized by its unique primary structure (5) and by an unusual substrate selectivity that is directed toward phosphate groups rather than unmodified amino acids (9, 10).Many proteins are in vitro substrates of CK1, including cytoskeletal proteins (myosin, ankyrin, troponin, spectrin, protein 4.1, and neural filament proteins), proteins involved in mRNA translation (tRNA synthetases and initiation factors 4B, 4E, and 51, signaling molecules (insulin receptor, the regulatory subunit of protein phosphatase-1, erythrocyte anion transporter), enzymes involved in nucleic acid metabolism (SV40 T-antigen, RNA polymerase I and 11, and p53), and metabolic enzymes such as glycogen synthase and acetyl-CoAcarboxylase (1).However, correlation of CK1-specific phosphorylation sites with sites phosphorylated in vivo is available only for SV40 T-antigen ( l l ) , glycogen synthase (12, 13), and the transcriptional regulators CREM (14) and p53 (15).CK1 phosphoryla-