Identification of a novel human tankyrase through its interaction with theadaptor protein Grb14

Tankyrase is an ankyrin repeat-containing poly(ADP-ribose) polymerase origi nally isolated as a binding partner for the telomeric protein TRF1, but rec ently identified as a mitogen-activated protein kinase substrate implicated in regulation of Golgi vesicle trafficking. In this study, a novel human t ankyrase, designated tankyrase 2, was isolated in a yeast two-hybrid screen as a binding partner for the Src homology 2 domain-containing adaptor prot ein Grb14. Tankyrase 2 is a 130-kDa protein, which lacks the N-terminal his tidine/proline/serine-rich region of tankyrase, but contains a correspondin g ankyrin repeat region, sterile alpha motif module, and poly(ADP-ribose) p olymerase homology domain. The TANKYRASE 2 gene localizes to chromosome 10q 23.2 and is widely expressed, with mRNA transcripts particularly abundant i n skeletal muscle and placenta. Upon subcellular fractionation, both Grb14 and tankyrase 2 associate with the low density microsome fraction, and asso ciation of these proteins in vivo can be detected by co-immunoprecipitation analysis. Deletion analyses implicate the N-terminal 110 amino acids of Gr b14 and ankyrin repeats 10-19 of tankyrase 2 in mediating this interaction, This study supports a role for the tankyrases in cytoplasmic signal transd uction pathways and suggests that vesicle trafficking may be involved in th e subcellular localization or signaling function of Grb14.