Association of SH2-B to phosphorylated tyrosine residues in the activation loop of TrkB.
Neurotrophins are essential for the survival and differentiation of neurons in the central and peripheral nervous systems. The binding of neurotrophins to their Trk receptors induces autophosphorylation of tyrosine residues and activation of several signaling components. However, the downstream signaling cascades remain to be fully elucidated. Here we describe molecular cloning of human SH2-B alpha, PH and SH2-domain-containing adaptor protein, as a TrkB binding protein, and how SH2-B alpha associate with the cytoplasmic domain of TrkB at phosphorylated tyrosine residues in the kinase activation loop. There was no distinct inhibitory or inducing effect on kinase activity detected by either a full-length or an SH2 domain of SH2-B alpha in vitro, even though the regulation mechanism of the activation loop on tyrosine kinase activity has been described. In addition to SH2-B alpha, the expression of three SH2-B alternative splice variants, SH2-B beta, gamma and delta, was detected in human cell lines. These splicing variants have unique carboxyl-terminal amino acid sequences due to insertion sequences as well as reading frameshifts.
Suzuki
Kenji
K
Novartis Pharma K.K., Tsukuba Research Institute, Tsukuba, Ibaraki 300-2611, Japan. suzukike@kyorin-u.ac.jp
Mizutani
Masaharu
M
Hitomi
Yoshiaki
Y
Kizaki
Takako
T
Ohno
Hideki
H
Ishida
Hitoshi
H
Haga
Shukoh
S
Koizumi
Shinichi
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation; D020813:Receptor, trkB / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014443:Tyrosine / Q000378:metabolism*; D018909:src Homology Domains
D017931:DNA Primers; D014443:Tyrosine; D020813:Receptor, trkB