DOI: 10.1073/pnas.94.22.12168. Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity

10.1073/pnas.94.22.12168

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Synapsin I is a synaptic vesicle-associated phosphoprotein that has been implicated in the formation of presynaptic specializations and in the regulation of neurotransmitter release. The nonreceptor tyrosine kinase c-Src is enriched on synaptic vesicles, where it accounts for most of the vesicle-associated tyrosine kinase activity. Using overlay, affinity chromatography, and coprecipitation assays, we have now shown that synapsin I is the major binding protein for the Src homology 3 (SH3) domain of c-Src in highly purified synaptic vesicle preparations. The interaction was mediated by the proline-rich domain D of synapsin I and was not significantly affected by stoichiometric phosphorylation of synapsin I at any of the known regulatory sites. The interaction of purified c-Src and synapsin I resulted in a severalfold stimulation of tyrosine kinase activity and was antagonized by the purified c-Src-SH3 domain. Depletion of synapsin I from purified synaptic vesicles resulted in a decrease of endogenous tyrosine kinase activity. Portions of the total cellular pools of synapsin I and Src were coprecipitated from detergent extracts of rat brain synaptosomal fractions using antibodies to either protein species. The interaction between synapsin I and c-Src, as well as the synapsin I-induced stimulation of tyrosine kinase activity, may be physiologically important in signal transduction and in the modulation of the function of axon terminals, both during synaptogenesis and at mature synapses.

Bibliography

Onofri, F., GiovedÃ¬, S., Vaccaro, P., Czernik, A. J., Valtorta, F., De Camilli, P., Greengard, P., & Benfenati, F. (1997). Synapsin I interacts with c-Src and stimulates its tyrosine kinaseâactivity. Proceedings of the National Academy of Sciences, 94(22), 12168â12173.

Authors 8

Franco Onofri (first)
Silvia Giovedì (additional)
Paola Vaccaro (additional)
Andrew J. Czernik (additional)
Flavia Valtorta (additional)
Pietro De Camilli (additional)
Paul Greengard (additional)
Fabio Benfenati (additional)

References 51 Referenced 59

10.1073/pnas.91.14.6486
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M T Brown, J A Cooper Biochim Biophys Acta 1287, 121–149 (1996). / Biochim Biophys Acta by Brown M T (1996)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:31 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:22 p.m.)
Indexed	1 year, 7 months ago (Jan. 11, 2024, 12:23 a.m.)
Issued	27 years, 10 months ago (Oct. 28, 1997)
Published	27 years, 10 months ago (Oct. 28, 1997)
Published Online	27 years, 10 months ago (Oct. 28, 1997)
Published Print	27 years, 10 months ago (Oct. 28, 1997)

Funders 0

None

BibTeX

@article{Onofri_1997, title={Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.22.12168}, DOI={10.1073/pnas.94.22.12168}, number={22}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Onofri, Franco and Giovedì, Silvia and Vaccaro, Paola and Czernik, Andrew J. and Valtorta, Flavia and De Camilli, Pietro and Greengard, Paul and Benfenati, Fabio}, year={1997}, month=oct, pages={12168–12173} }

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}