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

Related outputs

Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B
Vögtle, T., Sharma, S., Mori, J., Nagy, Z., Semeniak, D., Scandola, C., Geer, M., Smith, C., Lane, J., Pollack, S., Lassila, R., Jouppila, A., Barr, A.J., Ogg, D., Howard, T., McMiken, H., Warwicker, J., Geh, C., Rowlinson, R., Abbott, W., Eckly, A., Schulze, H., Wright, G., Mazharian, A., Fütterer, K., Rajesh, S., Douglas, M. and Senis, Y. 2019. Heparan sulfates are critical regulators of the inhibitory megakaryocyte-platelet receptor G6b-B. eLife. 2019;8 (e46840). doi:10.7554/eLife.46840

JoVE Methods Collection Highlights: Protein-Protein Interactions
Barr, A.J. and Overduin, M. 2019. JoVE Methods Collection Highlights: Protein-Protein Interactions. Journal of Visualized Experiments. 148, p. e59816. doi:10.3791/59816

The biochemical basis of disease
Barr, A.J. 2018. The biochemical basis of disease. Essays in Biochemistry. 62 (5), pp. 619-642. doi:10.1042/EBC20170054

Congenital macrothrombocytopenia with focal myelofibrosis due to mutations in human G6b-B is rescued in humanized mice
Hofmann, I., Geer, M.J., Vögtle, T., Crispin, A., Campagna, D.R., Barr, A.J., Calicchio, M.L., Heising, S., van Geffen, J.P., Kuijpers, M.J.E., Heemskerk, J.W.M., Eble, J.A., Schmitz-Abe, K., Obeng, E.A., Douglas, M., Freson, K., Pondarré, C., Favier, R., Jarvis, G.E., Markianos, K., Turro, E., Ouwehand, W.H., Mazharian, A., Fleming, M.D. and Senis, Y. 2018. Congenital macrothrombocytopenia with focal myelofibrosis due to mutations in human G6b-B is rescued in humanized mice. Blood. 132, pp. 1399-1412. doi:10.1182/blood-2017-08-802769

Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out?
Senis, Y. A. and Barr, A.J. 2018. Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out? Molecules. 23 (3), pp. 569-585. doi:10.3390/molecules23030569

Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin
Dorofejeva, O. and Barr, A.J. 2017. Defining the molecular basis of interaction between R3 receptor-type protein tyrosine phosphatases and VE-cadherin. PLoS ONE. 12 (9 : e0184574.), pp. 1-23. doi:10.1371/journal.pone.0184574

Automatic Selection of Molecular Descriptors using Random Forest: Application to Drug Discovery
Cano, G., Garcia-Rodriguez, J., Garcia-Garcia, A, Perez-Sanchez, H., Benediktsson, J.A., Thapa, A. and Barr, A.J. 2016. Automatic Selection of Molecular Descriptors using Random Forest: Application to Drug Discovery. Expert Systems with Applications. 72, pp. 151-159. doi:10.1016/j.eswa.2016.12.008

Targeting protein tyrosine phosphatase SHP2 for therapeutic intervention
Butterworth, S., Overduin, M. and Barr, A.J. 2014. Targeting protein tyrosine phosphatase SHP2 for therapeutic intervention. Future Medicinal Chemistry. 6 (12), pp. 1423-1437. doi:10.4155/fmc.14.88

Functional Studies On Receptor-Type Protein Tyrosine Phosphatases Of The R3 Subgroup Using Bimolecular Fluorescence Complementation (BiFC) Assays
Dorofejeva, O., Dwek, M. and Barr, A.J. 2014. Functional Studies On Receptor-Type Protein Tyrosine Phosphatases Of The R3 Subgroup Using Bimolecular Fluorescence Complementation (BiFC) Assays . Pharmacology 2014. London 16 Dec 2014 British Pharmacological Society.

Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states
Shintre, C.A., Pike, A.C.W., Li, Q., Kim, J.I., Barr, A.J., Goubin, S., Shrestha, L., Yang, J., Berridge, G., Ross, J., Stansfeld, P.J., Sansom, M.S.P., Edwards, A.M., Bountra, C., Marsden, B., von Delft, F., Bullock, A.N., Gileadi, O., Burgess-Brown, N.A. and Carpenter, E.P. 2013. Structures of ABCB10, a human ATP-binding cassette transporter in apo- and nucleotide-bound states. Proceedings of the National Academy of Sciences. 110 (24), pp. 9710-9715. doi:10.1073/pnas.1217042110

Receptor tyrosine phosphatase PTPγ is a regulator of spinal cord neurogenesis
Hashemia, H., Hurley, M., Gibson, A., Panova, V., Tchetchelnitski, V., Barr, A.J. and Stoker, A.W. 2011. Receptor tyrosine phosphatase PTPγ is a regulator of spinal cord neurogenesis. Molecular and Cellular Neuroscience. 46 (2), pp. 469-482. doi:10.1016/j.mcn.2010.11.012

Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class
Salah, E., Ugochukwu, E., Barr, A.J., von Delft, F., Knapp, S. and Elkins, J.M. 2011. Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. Journal of Medicinal Chemistry. 54 (7), pp. 2359-2367. doi:10.1021/jm101506n

Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development
Barr, A.J. 2010. Protein tyrosine phosphatases as drug targets: strategies and challenges of inhibitor development. Future Medicinal Chemistry. 2 (10), pp. 1563-1576. doi:10.4155/fmc.10.241

CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases
Ellison, S., Mori, J., Barr, A.J. and Senis, Y.A. 2010. CD148 enhances platelet responsiveness to collagen by maintaining a pool of active Src family kinases. Journal of Thrombosis and Haemostasis. 8 (7), pp. 1575-1583. doi:10.1111/j.1538-7836.2010.03865.x

Large-scale structural analysis of the classical human protein tyrosine phosphatome
Barr, A.J., Ugochukwu, E., Lee, W.H., King, O.N.F., Filippakopoulos, P., Alfano, I., Savitsky, P., Burgess-Brown, N.A., Muller, S. and Knapp, S. 2009. Large-scale structural analysis of the classical human protein tyrosine phosphatome. Cell. 136 (2), pp. 352-363. doi:10.1016/j.cell.2008.11.038

Large scale structural analysis of protein tyrosine phosphatases
Barr, A.J. and Knapp, S. 2009. Large scale structural analysis of protein tyrosine phosphatases. in: Bradshaw, R. and Dennis, E. (ed.) Handbook of cell signaling (2nd edition) San Diego, CA Elsevier. pp. 871-876

Sequence-specific 1H, 13C and 15N backbone resonance assignments of the 34 kDa catalytic domain of human PTPN7
Jeeves, M., McClelland, D.M., Barr, A.J. and Overduin, M. 2008. Sequence-specific 1H, 13C and 15N backbone resonance assignments of the 34 kDa catalytic domain of human PTPN7. Biomolecular NMR Assignments. 2 (2), pp. 101-103. doi:10.1007/s12104-008-9095-7

MAPK-specific tyrosine phosphatases: new targets for drug discovery?
Barr, A.J. and Knapp, S. 2006. MAPK-specific tyrosine phosphatases: new targets for drug discovery? Trends in Pharmacological Sciences. 27 (10), pp. 525-530. doi:10.1016/j.tips.2006.08.005

The crystal structure of human receptor protein tyrosine phosphatase κ phosphatase domain 1
Eswaran, J., Debreczeni, J.E., Longman, E., Barr, A.J. and Knapp, S. 2006. The crystal structure of human receptor protein tyrosine phosphatase κ phosphatase domain 1. Protein Science. 15 (6), pp. 1500-1505. doi:10.1110/ps.062128706

Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution
Barr, A.J., Debreczeni, J.E., Eswaran, J. and Knapp, S. 2006. Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution. Proteins. 63 (4), pp. 1132-1136. doi:10.1002/prot.20958

Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases
Eswaran, J., von Kries, J.P., Marsden, B., Longman, E., Debreczeni, J.E., Ugochukwu, E., Turnbull, A., Lee, W.H., Knapp, S. and Barr, A.J. 2006. Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases. Biochemical Journal. 395 (3), pp. 483-491. doi:10.1042/BJ20051931

Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3
Barr, A.J., Marjoram, R.J., Xu, J. and Snyderman, R. 2002. Phospholipase C-β 2 interacts with mitogen-activated protein kinase kinase 3. Biochemical and Biophysical Research Communications. 293 (1), pp. 647-652. doi:10.1016/S0006-291X(02)00259-0

RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses
Richardson, R.M., Marjoram, R.J., Barr, A.J. and Snyderman, R. 2001. RGS4 inhibits platelet-activating factor receptor phosphorylation and cellular responses. Biochemistry. 40 (12), pp. 3583-3588. doi:10.1021/bi0019242

Insect Cell systems to Study the Communication of Mammalian Receptors and G proteins
Windh, R., Barr, A.J. and Manning, D.R. 2000. Insect Cell systems to Study the Communication of Mammalian Receptors and G proteins. in: Kenakin, T. and Angus, J.A. (ed.) The Pharmacology of Functional, Biochemical, and Recombinant Receptor Systems Berlin Heidelberg Springer. pp. 335-362

Function and regulation of chemoattractant receptors
Haribabu, B., Richardson, R.M., Verghese, M.W., Barr, A.J., Zhelev, D.V. and Snyderman, R. 2000. Function and regulation of chemoattractant receptors. Immunologic Research. 22 (2-3), pp. 271-279. doi:10.1385/IR:22:2-3:271

Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits
Barr, A.J., Ali, H., Haribabu, B., Snyderman, R. and Smrcka, A.V. 2000. Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits. Biochemistry. 39 (7), pp. 1800-1806. doi:10.1021/bi992021f

Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins
Windh, R., Lee, M.J., Hla, T., An, S., Barr, A.J. and Manning, D.R. 1999. Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the Gi, Gq, and G12 families of heterotrimeric G proteins. Journal of Biological Chemistry. 274 (39), pp. 27351-27358. doi:10.1074/jbc.274.39.27351

Agonist-promoted GTP[S35]-binding as a probe for receptor.G protein communication in Sf9 cells
Barr, A.J. and Manning, D.R. 1999. Agonist-promoted GTP[S35]-binding as a probe for receptor.G protein communication in Sf9 cells. in: Manning, D.R. (ed.) G proteins: techniques of analysis Boca Raton, FL CRC Press. pp. 227-246

Differential regulation of formyl peptide and platelet-activating factor receptors: role of phospholipase Cbeta3 phosphorylation by protein kinase A
Ali, H., Sozzani, S., Fisher, I., Barr, A.J., Richardson, R.M., Haribabu, B. and Snyderman, R. 1998. Differential regulation of formyl peptide and platelet-activating factor receptors: role of phospholipase Cbeta3 phosphorylation by protein kinase A. Journal of Biological Chemistry. 273 (18), pp. 11012-11016. doi:10.1074/jbc.273.18.11012

Agonist-independent activation of Gz by the 5-hydroxytryptamine1A receptor co-expressed in spodoptera frugiperda cells: distinguishing inverse agonists from neutral antagonists
Barr, A.J. and Manning, D.R. 1997. Agonist-independent activation of Gz by the 5-hydroxytryptamine1A receptor co-expressed in spodoptera frugiperda cells: distinguishing inverse agonists from neutral antagonists. Journal of Biological Chemistry. 272 (52), pp. 32979-32987. doi:10.1074/jbc.272.52.32979

Reconstitution of receptors and GTP-binding regulatory proteins (G Proteins) in Sf9 Cells: a direct evaluation of selectivity in receptor.G protein coupling
Barr, A.J., Brass, L.F. and Manning, D.R. 1997. Reconstitution of receptors and GTP-binding regulatory proteins (G Proteins) in Sf9 Cells: a direct evaluation of selectivity in receptor.G protein coupling. Journal of Biological Chemistry. 272 (4), pp. 2223-2229. doi:10.1074/jbc.272.4.2223

Protein kinase C mediates delayed inhibitory feedback regulation of human neurokinin type 1 receptor activation of phospholipase C in UC11 astrocytoma cells
Barr, A.J. and Watson, S.P. 1994. Protein kinase C mediates delayed inhibitory feedback regulation of human neurokinin type 1 receptor activation of phospholipase C in UC11 astrocytoma cells. Molecular Pharmacology. 46 (2), pp. 266-273.

Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors
Barr, A.J. and Watson, S.P. 1993. Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors. British Journal of Pharmacology. 108 (1), pp. 223-227.

The presence of NK3 tachykinin receptors on rat uterus
Barr, A.J., Watson, S.P., Bernal, A.L. and Nimmo, A.J. 1991. The presence of NK3 tachykinin receptors on rat uterus. European Journal of Pharmacology. 203 (2), pp. 287-290. doi:10.1016/0014-2999(91)90726-7

Permalink - https://westminsterresearch.westminster.ac.uk/item/90x37/hd-ptp-is-a-catalytically-inactive-tyrosine-phosphatase-due-to-a-conserved-divergence-in-its-phosphatase-domain


Share this
Tweet
Email