Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain

Jesús Mariano Ureña, Anna La Torre Vila, Albert Martínez, Eve Lowenstein, Neus Franco, Raphaelle Winsky-Sommerer, Xavier Fontana, Ricardo Casaroli-Marano, Miguel Angel Ibáñez-Sabio, Marta Pascual, José Antonio Del Rio, Luis De Lecea, Eduardo Soriano

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Cytosolic tyrosine kinases play a critical role both in neural development and in adult brain function and plasticity. Here we isolated a cDNA with high homology to human Ack1 and mouse Tnk2. This cDNA directs the expression of a 125-kD protein that can be autophosphorylated in tyrosines. Initially, this clone was named Pyk1 for proline-rich tyrosine kinase (Lev et al., 1995); however, since it corresponds to the mouse homolog of Ack1, here we called it Ack1/Pyk1. In this study we show that Ack1/Pyk1 mRNA and protein is highly expressed in the developing and adult brain. The highest levels of Ack1/Pyk1 expression were detected in the hippocampus, neocortex, and cerebellum. Electron microscopy studies showed that Ack1/Pyk1 protein is expressed in these regions both at dendritic spines and presynaptic axon terminals, indicating a role in synaptic function. Furthermore, we demonstrate that Ack1/Pyk1 mRNA levels are strongly upregulated by increased neural activity, produced by intraperitoneal kainate injections. During development, Ack1/Pyk1 was also expressed in the proliferative ventricular zones and in postmitotic maturing neurons. In neuronal cultures, Ack1/Pyk1 was detected in developing dendrites and axons, including dendritic tips and growth cones. Moreover, Ack1/Pyk1 colocalized with Cdc42 GTPase in neuronal cultures and coimmunoprecipitated with Cdc42 in HEK 293T cells. Altogether, our findings indicate that Ack1/Pyk1 tyrosine kinase may be involved both in adult synaptic function and plasticity and in brain development.

Original languageEnglish (US)
Pages (from-to)119-132
Number of pages14
JournalJournal of Comparative Neurology
Volume490
Issue number2
DOIs
StatePublished - Sep 19 2005
Externally publishedYes

Keywords

  • Associating proteins
  • Phosphorylatlon
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ureña, J. M., La Torre Vila, A., Martínez, A., Lowenstein, E., Franco, N., Winsky-Sommerer, R., Fontana, X., Casaroli-Marano, R., Ibáñez-Sabio, M. A., Pascual, M., Del Rio, J. A., De Lecea, L., & Soriano, E. (2005). Expression, synaptic localization, and developmental regulation of Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing and adult brain. Journal of Comparative Neurology, 490(2), 119-132. https://doi.org/10.1002/cne.20656