HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain

Gingras, M.C., Zhang, Y.L., Kharitidi, D., Barr, A.J., Knapp, S., Tremblay, M.L. and Pause, A. 2009. HD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain. PLoS ONE. Online.

TitleHD-PTP is a catalytically inactive tyrosine phosphatase due to a conserved divergence in its phosphatase domain
AuthorsGingras, M.C., Zhang, Y.L., Kharitidi, D., Barr, A.J., Knapp, S., Tremblay, M.L. and Pause, A.
Abstract

Background

The HD-PTP protein has been described as a tumor suppressor candidate and based on its amino acid sequence, categorized as a classical non-transmembrane protein tyrosine phosphatase (PTP). To date, no HD-PTP phosphorylated substrate has been identified and controversial results concerning its catalytic activity have been recently reported.

Methodology and Results

Here we report a rigorous enzymatic analysis demonstrating that the HD-PTP protein does not harbor tyrosine phosphatase or lipid phosphatase activity using the highly sensitive DiFMUP substrate and a panel of different phosphatidylinositol phosphates. We found that HD-PTP tyrosine phosphatase inactivity is caused by an evolutionary conserved amino acid divergence of a key residue located in the HD-PTP phosphatase domain since its back mutation is sufficient to restore the HD-PTP tyrosine phosphatase activity. Moreover, in agreement with a tumor suppressor activity, HD-PTP expression leads to colony growth reduction in human cancer cell lines, independently of its catalytic PTP activity status.

Conclusion

In summary, we demonstrate that HD-PTP is a catalytically inactive protein tyrosine phosphatase. As such, we identify one residue involved in its inactivation and show that its colony growth reduction activity is independent of its PTP activity status in human cancer cell lines.

JournalPLoS ONE
Journal citationOnline
ISSN1932-6203
Year2009
PublisherPublic Library of Science
Web address (URL)http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005105
Publication dates
Published2009

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