QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, January 26, 2005, 25(4):880-888; doi:10.1523/JNEUROSCI.4365-04.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Chen, B. Articles by Bixby, J. L. Search for Related Content PubMed PubMed Citation Articles by Chen, B. Articles by Bixby, J. L.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
A Novel Substrate of Receptor Tyrosine Phosphatase PTPRO Is Required for Nerve Growth Factor-Induced Process Outgrowth

Bo Chen¹ and John L. Bixby^1,2,3

Departments of ¹Molecular and Cellular Pharmacology and ²Neurological Surgery and ³Neuroscience Program, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33136

The receptor protein tyrosine phosphatase PTPRO may be involved in axon guidance both as a ligand and as a neuronal receptor. We have begun to characterize signaling by PTPRO as a receptor by screening for proteins interacting with the intracellular domain of PTPRO. In a yeast-two hybrid screen, we identified a novel class of protein, which we named neuronal pentraxin with chromo domain (NPCD), as a PTPRO-interacting protein. We have shown recently that NPCD has multiple cytoplasmic isoforms as a result of alternative splicing and that these proteins are present in many neurons, mainly associated with the inner side of the plasma membrane. Through additional two-hybrid experiments, cotransfection and reciprocal coprecipitation, glutathione S-transferase pulldown, and immunoprecipitation in vivo, we confirm that NPCD isoforms interact with the catalytic phosphatase domain of PTPRO. We also find that at least one NPCD isoform is tyrosine phosphorylated in vivo and can serve as a substrate for PTPRO in vitro. Analysis of PTPRO knock-out mice demonstrates that normal localization of NPCD at the plasma membrane requires PTPRO expression, suggesting a physiological role for the NPCD/PTPRO interaction. NPCD is likely to be relevant to axon growth and/or guidance, because RNA interference mediated knock-down of NPCD expression in pheochromocytoma cells inhibits NGF-induced neuronal process outgrowth without affecting NGF-dependent survival or initial NGF signaling.

Key words: tyrosine phosphorylation; neurite outgrowth; pentraxin; chromo domain; PC12; neuronal differentiation; nerve growth factor

---

Received Oct 20, 2004; revised November 29, 2004; accepted December 7, 2004.

This article has been cited by other articles:

				M. A. Abad, M. Enguita, N. DeGregorio-Rocasolano, I. Ferrer, and R. Trullas Neuronal Pentraxin 1 Contributes to the Neuronal Damage Evoked by Amyloid-{beta} and Is Overexpressed in Dystrophic Neurites in Alzheimer's Brain J. Neurosci., December 6, 2006; 26(49): 12735 - 12747. [Abstract] [Full Text] [PDF]

				L. Stepanek, A. W. Stoker, E. Stoeckli, and J. L. Bixby Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development J. Neurosci., April 13, 2005; 25(15): 3813 - 3823. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help