Sap-1/PTPRH activity is regulated by reversible dimerization

Sap-1/PTPRH, a receptor protein tyrosine phosphatase (RPTP), is a ubiquitously expressed enzyme that is upregulated in human gastrointestinal cancers. Using both chemical cross-linkers and co-immunoprecipitation we show that overexpressed full-length Sap-1 is present as a stable homodimer. Unlike a...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-06, Vol.331 (2), p.497-502
Main Authors: Wälchli, Sébastien, Espanel, Xavier, van Huijsduijnen, Rob Hooft
Format: Article
Language:English
Subjects:
Animals
Catalytic Domain
COS Cells
Cross-Linking Reagents - chemistry
Cross-Linking Reagents - metabolism
Cysteine - genetics
Cysteine - metabolism
Dimerization
Gene Expression
Protein Structure, Quaternary
Protein Structure, Tertiary
Protein tyrosine phosphatase
Protein Tyrosine Phosphatases - chemistry
Protein Tyrosine Phosphatases - genetics
Protein Tyrosine Phosphatases - metabolism
Receptors, Cell Surface - chemistry
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Sap-1
Sequence Deletion - genetics
Signaling cascade
Structure-Activity Relationship
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Summary:Sap-1/PTPRH, a receptor protein tyrosine phosphatase (RPTP), is a ubiquitously expressed enzyme that is upregulated in human gastrointestinal cancers. Using both chemical cross-linkers and co-immunoprecipitation we show that overexpressed full-length Sap-1 is present as a stable homodimer. Unlike a number of adhesion RPTPs which have tandem catalytic domains that are involved in dimerization, Sap-1 has a single catalytic domain, and we show that this domain is not required for Sap-1 dimerization, which is mediated instead by the large extracellular and transmembrane domains. Exposing cells that express the receptor to a reducing environment reversibly disrupts the Sap-1 dimer, suggesting that cysteine bonds play a role in dimer formation/stabilization. The switch between Sap-1 dimers and monomers is accompanied by an increase in catalytic activity as judged by its capacity to dephosphorylate and activate c-src, which we identify as a novel substrate for this phosphatase.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.03.196