Association of the Src family tyrosine kinase Fyn with TrkB.

Fyn tyrosine kinase, a member of the Src family, was recently reported to be present in neurons and glia cells. We investigated whether Fyn is involved in the Trk-dependent signal transduction pathways of neurotrophin. The Fyn-Src homology domain 2 (SH2) was observed to associate in vitro with the intracellular domain ...
of TrkB (ICD-TrkB). This association was dependent on the autophosphorylation of ICD-TrkB. The Fyn-SH2 domains bound to phosphorylated ICD-TrkB (pICD-TrkB) with an affinity similar to the binding of phospholipase Cgamma (PLCgamma)-SH2 domains to its autophosphorylation site in TrkB. The Src-SH2 domains showed substantially lower affinity with pICD-TrkB, suggesting that the association between Fyn-SH2 and pICD-TrkB is not due to nonspecific interactions of SH2 domains with phosphorylated tyrosine residues. This is further supported by the observation that Fyn-SH2 was able to trap phosphorylated TrkB in cell lysate prepared from primary rat cortical neurons stimulated with brain-derived neurotrophic factor (BDNF). In contrast, endogenous Fyn was coprecipitated with TrkB from cortical neurons without BDNF stimulation. This basal association showed a threefold increase on BDNF stimulation, probably due to the SH2/phosphotyrosine interaction that was observed in the cell-free system. All these data suggest the involvement of Fyn in the neurotrophin signal transduction pathways downstream of TrkB.
Mesh Terms:
Animals, Baculoviridae, Brain-Derived Neurotrophic Factor, Cells, Cultured, Cerebral Cortex, Insects, Long-Term Potentiation, Neurons, Neuroprotective Agents, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Rats, Receptor Protein-Tyrosine Kinases, Receptor, Ciliary Neurotrophic Factor, Receptors, Nerve Growth Factor, Signal Transduction, src Homology Domains
J. Neurochem.
Date: Jul. 01, 1998
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