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Journal of Biochemistry Advance Access published online on July 23, 2007
Journal of Biochemistry, doi:10.1093/jb/mvm140
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© 2007 The Japanese Biochemical Society

Tyrosine Phosphorylation of ErbB4 Is Enhanced by PSD95 and Repressed by Protein Tyrosine Phosphatase Receptor Type Z

Akihiro Fujikawa1, Jeremy Pak Hong Chow1,2, Hidetada Shimizu1,2, Masahide Fukada1, Ryoko Suzuki1 and Masaharu Noda1,2,*

1Division of Molecular Neurobiology, National Institute for Basic Biology, and 2School of Life Science, The Graduate University for Advanced Studies, 5-1 Higashiyama, Myodaiji-cho, Okazaki, Aichi 444-8787, Japan.

*To whom correspondence should be addressed. Tel: +81-564-59-5846, Fax: +81-564-59-5845, E-mail: madon{at}nibb.ac.jp

Received June 5, 2007; Accepted June 22, 2007


  Abstract

Protein tyrosine phosphatase receptor type Z (Ptprz/PTP{zeta}/RPTPß) is a receptor-like protein tyrosine phosphatase (RPTP) preferentially expressed in the brain. ErbB4 is a member of the ErbB-family tyrosine kinases known as a neuregulin (NRG) receptor. Both are known to bind to postsynaptic density-95 (PSD95) on the second and the first/second PDZ (PSD95/Disc large/zona occludens1) domains, respectively, through the PDZ-binding motif of their carboxyl termini. Here we report a functional interaction between Ptprz and ErbB4. An intracellular carboxyl-terminal region of Ptprz pulled-down PSD95 and ErbB4 from an adult rat synaptosomal preparation. ErbB4 and Ptprz showed colocalization in cell bodies and apical dendrites of neurons in the prefrontal cortex. In HEK293T cells, phosphorylation of ErbB4 was raised by coexpression of PSD95, which was repressed by additional expression of Ptprz. In vitro experiments using the whole intracellular region (ICR) of ErbB4 also showed that PSD95 stimulates the autophosphorylation of ErbB4, and that the ICR of Ptprz dephosphorylates ErbB4 independent of the presence of PSD95. Taken together with the finding that the tyrosine phosphorylation level of ErbB4 was increased in Ptprz-deficient mice, these results suggest that Ptprz has a role in suppressing the autoactivation of ErbB4 by PSD95 at the postsynaptic density in the adult brain.

Key Words: ErbB4, PDZ domain, PSD-95/SAP90 family, Ptprz/PTP{zeta}/RPTPß, tyrosine phosphorylation


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