Identification of a Novel Human Tankyrase through Its Interaction with the Adaptor Protein Grb14

• Published in: The Journal of biological chemistry 2001-05, Vol.276 (20), p.17172-17180
• Main Authors: Lyons, Ruth J., Deane, Róisı́n, Lynch, Danielle K., Ye, Zheng-Sheng Jeffrey, Sanderson, Georgina M., Eyre, Helen J., Sutherland, Grant R., Daly, Roger J.
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Binding Sites; Cell Line; Chromatography, Affinity; Chromosome Mapping; Chromosomes, Human, Pair 10; Cloning, Molecular; Gene Library; Glutathione Transferase - metabolism; Humans; In Situ Hybridization, Fluorescence; Molecular Sequence Data; Poly(ADP-ribose) Polymerases - chemistry; Poly(ADP-ribose) Polymerases - genetics; Poly(ADP-ribose) Polymerases - metabolism; Proteins - chemistry; Proteins - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - isolation & purification; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - genetics; Sequence Alignment; Sequence Homology, Amino Acid; Tankyrases
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M009756200

Tankyrase is an ankyrin repeat-containing poly(ADP-ribose) polymerase originally isolated as a binding partner for the telomeric protein TRF1, but recently identified as a mitogen-activated protein kinase substrate implicated in regulation of Golgi vesicle trafficking. In this study, a novel human tankyrase, designated tankyrase 2, was isolated in a yeast two-hybrid screen as a binding partner for the Src homology 2 domain-containing adaptor protein Grb14. Tankyrase 2 is a 130-kDa protein, which lacks the N-terminal histidine/proline/serine-rich region of tankyrase, but contains a corresponding ankyrin repeat region, sterile α motif module, and poly(ADP-ribose) polymerase homology domain. TheTANKYRASE 2 gene localizes to chromosome 10q23.2 and is widely expressed, with mRNA transcripts particularly abundant in skeletal muscle and placenta. Upon subcellular fractionation, both Grb14 and tankyrase 2 associate with the low density microsome fraction, and association of these proteins in vivo can be detected by co-immunoprecipitation analysis. Deletion analyses implicate the N-terminal 110 amino acids of Grb14 and ankyrin repeats 10–19 of tankyrase 2 in mediating this interaction. This study supports a role for the tankyrases in cytoplasmic signal transduction pathways and suggests that vesicle trafficking may be involved in the subcellular localization or signaling function of Grb14. AF329696