TTIP is a novel protein that interacts with the truncated T1 TrkB neurotrophin receptor

Alternative splicing of the TrkB gene produces a full length tyrosine kinas e receptor as well as two truncated isoforms that contain extracellular and transmembrane domains but lack the kinase domain and have unique C termina l tails. The function of the truncated TrkB isoforms is unclear and to gain insights into their function, we have isolated a protein from 15N neurobla stoma cells that specifically binds the TrkB.T1 isoform, Pulldown experimen ts using a GST fusion protein containing the TrkB.T1 intracellular domain i dentified a 61 kDa protein from radiolabeled 15N lysates. Coimmunoprecipita tion experiments showed that the 61 kDa protein interacted with epitope-tag ged TrkB.T1 overexpressed in 15N cells as well as with TrkB.T1 which was en dogenously expressed. Peptide competition experiments revealed that the pro tein, designated TTIP (for Truncated TrkB Interacting Protein), showed spec ific binding to the TrkB.T1 tail. Mauldi MS and MS/MS analysis has revealed that TTIP is a novel protein not Set listed in the current databases. (C) 2000 Academic Press.