Striatal-enriched Protein-tyrosine Phosphatase (STEP) Regulates Pyk2 Kinase Activity

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 May 1

PMID 22544749

Citations 53

Authors

Jian Xu

Pradeep Kurup

Jason A Bartos

Tommaso Patriarchi

Johannes W Hell

Paul J Lombroso

Affiliations

Soon will be listed here.

Abstract

Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family and is highly expressed in brain and hematopoietic cells. Pyk2 plays diverse functions in cells, including the regulation of cell adhesion, migration, and cytoskeletal reorganization. In the brain, it is involved in the induction of long term potentiation through regulation of N-methyl-d-aspartate receptor trafficking. This occurs through the phosphorylation and activation of Src family tyrosine kinase members, such as Fyn, that phosphorylate GluN2B at Tyr(1472). Phosphorylation at this site leads to exocytosis of GluN1-GluN2B receptors to synaptic membranes. Pyk2 activity is modulated by phosphorylation at several critical tyrosine sites, including Tyr(402). In this study, we report that Pyk2 is a substrate of striatal-enriched protein-tyrosine phosphatase (STEP). STEP binds to and dephosphorylates Pyk2 at Tyr(402). STEP KO mice showed enhanced phosphorylation of Pyk2 at Tyr(402) and of the Pyk2 substrates paxillin and ASAP1. Functional studies indicated that STEP opposes Pyk2 activation after KCl depolarization of cortical slices and blocks Pyk2 translocation to postsynaptic densities, a key step required for Pyk2 activation and function. This is the first study to identify Pyk2 as a substrate for STEP.

Citing Articles

Impairment of neuronal tyrosine phosphatase STEP worsens post-ischemic inflammation and brain injury under hypertensive condition.

Paramasivam P, Choi S, Poddar R, Paul S J Neuroinflammation. 2024; 21(1):271.

PMID: 39438980 PMC: 11515672. DOI: 10.1186/s12974-024-03227-z.

Uncovering the Significance of STEP61 in Alzheimer's Disease: Structure, Substrates, and Interactome.

Bagwe P, Deshpande R, Juhasz G, Sathaye S, Joshi S Cell Mol Neurobiol. 2023; 43(7):3099-3113.

PMID: 37219664 PMC: 11410018. DOI: 10.1007/s10571-023-01364-2.

Sevoflurane exposure during the second trimester induces neurotoxicity in offspring rats by hyperactivation of PARP-1.

Wang C, Jiang Q, Zhao P Psychopharmacology (Berl). 2022; 239(9):3031-3045.

PMID: 35859039 DOI: 10.1007/s00213-022-06188-4.

The Non-receptor Tyrosine Kinase Pyk2 in Brain Function and Neurological and Psychiatric Diseases.

de Pins B, Mendes T, Giralt A, Girault J Front Synaptic Neurosci. 2021; 13:749001.

PMID: 34690733 PMC: 8527176. DOI: 10.3389/fnsyn.2021.749001.

The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.

Mahaman Y, Huang F, Embaye K, Wang X, Zhu F Front Cell Dev Biol. 2021; 9:680118.

PMID: 34195199 PMC: 8236946. DOI: 10.3389/fcell.2021.680118.

References

Sasaki H, Nagura K, Ishino M, Tobioka H, Kotani K, Sasaki T . Cloning and characterization of cell adhesion kinase beta, a novel protein-tyrosine kinase of the focal adhesion kinase subfamily. J Biol Chem. 1995; 270(36):21206-19. DOI: 10.1074/jbc.270.36.21206. View

Baum M, Kurup P, Xu J, Lombroso P . A STEP forward in neural function and degeneration. Commun Integr Biol. 2010; 3(5):419-22. PMC: 2974069. DOI: 10.4161/cib.3.5.12692. View

Kruljac-Letunic A, Moelleken J, Kallin A, Wieland F, Blaukat A . The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. J Biol Chem. 2003; 278(32):29560-70. DOI: 10.1074/jbc.M302278200. View

Derkinderen P, Siciliano J, Toutant M, Girault J . Differential regulation of FAK+ and PYK2/Cakbeta, two related tyrosine kinases, in rat hippocampal slices: effects of LPA, carbachol, depolarization and hyperosmolarity. Eur J Neurosci. 1998; 10(5):1667-75. DOI: 10.1046/j.1460-9568.1998.00174.x. View

Shiozuka K, Watanabe Y, Ikeda T, Hashimoto S, Kawashima H . Cloning and expression of PCPTP1 encoding protein tyrosine phosphatase. Gene. 1995; 162(2):279-84. DOI: 10.1016/0378-1119(95)00306-q. View

Ostergaard H, Lou O, Arendt C, Berg N . Paxillin phosphorylation and association with Lck and Pyk2 in anti-CD3- or anti-CD45-stimulated T cells. J Biol Chem. 1998; 273(10):5692-6. DOI: 10.1074/jbc.273.10.5692. View

Boulanger L, Lombroso P, Raghunathan A, During M, Wahle P, Naegele J . Cellular and molecular characterization of a brain-enriched protein tyrosine phosphatase. J Neurosci. 1995; 15(2):1532-44. PMC: 6577844. View

Hallett P, Spoelgen R, Hyman B, Standaert D, Dunah A . Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking. J Neurosci. 2006; 26(17):4690-700. PMC: 6674081. DOI: 10.1523/JNEUROSCI.0792-06.2006. View

Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X . DOG 1.0: illustrator of protein domain structures. Cell Res. 2009; 19(2):271-3. DOI: 10.1038/cr.2009.6. View

10.

Pulido R, Zuniga A, Ullrich A . PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ERK2 by association through a kinase interaction motif. EMBO J. 1998; 17(24):7337-50. PMC: 1171079. DOI: 10.1093/emboj/17.24.7337. View

11.

Valjent E, Pascoli V, Svenningsson P, Paul S, Enslen H, Corvol J . Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum. Proc Natl Acad Sci U S A. 2004; 102(2):491-6. PMC: 544317. DOI: 10.1073/pnas.0408305102. View

12.

Davidson D, Veillette A . PTP-PEST, a scaffold protein tyrosine phosphatase, negatively regulates lymphocyte activation by targeting a unique set of substrates. EMBO J. 2001; 20(13):3414-26. PMC: 125513. DOI: 10.1093/emboj/20.13.3414. View

13.

Du Q, Ren X, Xie Y, Wang Q, Mei L, Xiong W . Inhibition of PYK2-induced actin cytoskeleton reorganization, PYK2 autophosphorylation and focal adhesion targeting by FAK. J Cell Sci. 2001; 114(Pt 16):2977-87. DOI: 10.1242/jcs.114.16.2977. View

14.

Goebel-Goody S, Davies K, Alvestad Linger R, Freund R, Browning M . Phospho-regulation of synaptic and extrasynaptic N-methyl-d-aspartate receptors in adult hippocampal slices. Neuroscience. 2008; 158(4):1446-59. DOI: 10.1016/j.neuroscience.2008.11.006. View

15.

Dunah A, Sirianni A, Fienberg A, Bastia E, Schwarzschild M, Standaert D . Dopamine D1-dependent trafficking of striatal N-methyl-D-aspartate glutamate receptors requires Fyn protein tyrosine kinase but not DARPP-32. Mol Pharmacol. 2004; 65(1):121-9. DOI: 10.1124/mol.65.1.121. View

16.

Hemmings Jr H, Greengard P, Tung H, Cohen P . DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature. 1984; 310(5977):503-5. DOI: 10.1038/310503a0. View

17.

Dikic I, Tokiwa G, Lev S, Courtneidge S, Schlessinger J . A role for Pyk2 and Src in linking G-protein-coupled receptors with MAP kinase activation. Nature. 1996; 383(6600):547-50. DOI: 10.1038/383547a0. View

18.

Braithwaite S, Paul S, Nairn A, Lombroso P . Synaptic plasticity: one STEP at a time. Trends Neurosci. 2006; 29(8):452-8. PMC: 1630769. DOI: 10.1016/j.tins.2006.06.007. View

19.

Kumar S, Avraham S, Bharti A, Goyal J, Pandey P, Kharbanda S . Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1. J Biol Chem. 1999; 274(43):30657-63. DOI: 10.1074/jbc.274.43.30657. View

20.

Venkitaramani D, Paul S, Zhang Y, Kurup P, Ding L, Tressler L . Knockout of striatal enriched protein tyrosine phosphatase in mice results in increased ERK1/2 phosphorylation. Synapse. 2008; 63(1):69-81. PMC: 2706508. DOI: 10.1002/syn.20608. View