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tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCγ1 and Sam68

Oncogene volume 22, pages 8707–8715 (2003)Cite this article

Abstract

tr-kit is a truncated form of the tyrosine kinase receptor c-kit expressed in the haploid phase of spermatogenesis. Upon microinjection, tr-kit triggers metaphase-to-anaphase transition in mouse eggs by the sequential activation of Fyn and PLCγ1. Here, we show that tr-kit promotes the interaction of several tyrosine-phosphorylated proteins with the SH3 domain of PLCγ1. Western blot analysis indicates that one of these proteins is Sam68, an RNA-binding protein that is known to interact with and be phosphorylated by Src-like kinases in mitosis. tr-kit promotes the association of Sam68 with PLCγ1 and Fyn in a multimolecular complex, as demonstrated by co-immunoprecipitation of the phosphorylated forms of these proteins using antibodies directed to anyone of the partners of the complex. Expression of tr-kit potentiates the interaction of endogenous Sam68 also with the SH3 domain of Fyn. Furthermore, the subcellular localization of Sam68 is affected by tr-kit through activation of Fyn in live cells. Lastly, we show that interaction with the SH3 domain of Fyn triggers the release of Sam68 from bound RNA. Thus, our data suggest that tr-kit promotes the formation of a multimolecular complex composed of Fyn, PLCγ1 and Sam68, which allows phosphorylation of PLCγ1 by Fyn, and may modulate RNA metabolism.

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Acknowledgements

We thank Dr Marco Barchi for preparing some tr-kit expression vectors. This work was supported by grants from the Ministero Italiano Università e Ricerca (MIUR) cofin 2002 and Agenzia Spaziale Italiana (ASI).

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Authors and Affiliations

  1. Department of Public Health and Cell Biology, Section of Anatomy, University of Rome ‘Tor Vergata’, Rome, Italy

    Maria Paola Paronetto, Raffaele Geremia, Pellegrino Rossi & Claudio Sette

  2. Institute for Human Genetics, University of Newcastle Upon Tyne, Newcastle, UK

    Julian P Venables & David J Elliott

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  1. Maria Paola Paronetto
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  2. Julian P Venables
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  3. David J Elliott
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  4. Raffaele Geremia
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  5. Pellegrino Rossi
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  6. Claudio Sette
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Correspondence to Claudio Sette.

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Paronetto, M., Venables, J., Elliott, D. et al. tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCγ1 and Sam68. Oncogene 22, 8707–8715 (2003). https://doi.org/10.1038/sj.onc.1207016

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