TrkB mutant lacking the amino-terminal half of the extracellular portion acts as a functional brain-derived neurotrophic factor receptor.
A series of mutants with deletion in the extracellular portion of TrkB were expressed transiently and stably in mammalian cells to examine the brain-derived neurotrophic factor (BDNF)-binding properties of TrkB. We found that these binding activities were retained by the TrkB deletion mutant (TrkBDelta4) lacking most of the extracellular portion, cysteine-rich cluster 1 and 2, leucine-rich motif and most of the first immunoglobulin-like domain (Ig1). Furthermore, the results of the neurotrophin selectivity, the equilibrium binding constant, auto-phosphorylation and BDNF dependent cell survival indicate that TrkBDelta4 acts as a functional BDNF receptor comparable to wild-type TrkB. Thus, our findings showed that only the carboxyl-terminal half of the extracellular portion of TrkB, which includes the Ig2 domain, is essential for the functional BDNF receptor.
Kojima
S
S
Shionogi Institute for Medical Science, 2-5-1, Mishima, Settsu-shi, Osaka 566-0022, Japan.
Nakayama
T
T
Kuwajima
G
G
Suzuki
H
H
Sakata
T
T
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D019556:COS Cells; D066298:In Vitro Techniques; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011487:Protein Conformation; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion
D019208:Brain-Derived Neurotrophic Factor; D010446:Peptide Fragments; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D020794:Receptor Protein-Tyrosine Kinases