Brief Report

A Novel Regulatory Mechanism of MAP Kinases Activation and Nuclear Translocation Mediated by PKA and the PTP-SL Tyrosine Phosphatase

Correspondence to: Rafael Pulido, Instituto de Investigaciones Citológicas, Amadeo de Saboya, 4, 46010 Valencia, Spain. Tel:34-96-3391256 Fax:34-96-3601453 E-mail:rpulido{at}ochoa.fib.es.

Protein tyrosine phosphatase PTP-SL retains mitogen-activated protein (MAP) kinases in the cytoplasm in an inactive form by association through a kinase interaction motif (KIM) and tyrosine dephosphorylation. The related tyrosine phosphatases PTP-SL and STEP were phosphorylated by the cAMP-dependent protein kinase A (PKA). The PKA phosphorylation site on PTP-SL was identified as the Ser²³¹ residue, located within the KIM. Upon phosphorylation of Ser²³¹, PTP-SL binding and tyrosine dephosphorylation of the MAP kinases extracellular signal–regulated kinase (ERK)1/2 and p38 were impaired. Furthermore, treatment of COS-7 cells with PKA activators, or overexpression of the C catalytic subunit of PKA, inhibited the cytoplasmic retention of ERK2 and p38 by wild-type PTP-SL, but not by a PTP-SL S231A mutant. These findings support the existence of a novel mechanism by which PKA may regulate the activation and translocation to the nucleus of MAP kinases.

Key Words: MAP kinases, PKA, PTP-SL, tyrosine phosphatases, signal transduction

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Chuderland, D., Marmor, G., Shainskaya, A., Seger, R. (2008). Calcium-mediated Interactions Regulate the Subcellular Localization of Extracellular Signal-regulated Kinases. J. Biol. Chem. 283: 11176-11188 [Abstract] [Full Text]  
• Tarrega, C., Rios, P., Cejudo-Marin, R., Blanco-Aparicio, C., van den Berk, L., Schepens, J., Hendriks, W., Tabernero, L., Pulido, R. (2005). ERK2 Shows a Restrictive and Locally Selective Mechanism of Recognition by Its Tyrosine Phosphatase Inactivators Not Shared by Its Activator MEK1. J. Biol. Chem. 280: 37885-37894 [Abstract] [Full Text]  
• Lecureuil, C., Tesseraud, S., Kara, E., Martinat, N., Sow, A., Fontaine, I., Gauthier, C., Reiter, E., Guillou, F., Crepieux, P. (2005). Follicle-Stimulating Hormone Activates p70 Ribosomal Protein S6 Kinase by Protein Kinase A-Mediated Dephosphorylation of Thr 421/Ser 424 in Primary Sertoli Cells. Mol. Endocrinol. 19: 1812-1820 [Abstract] [Full Text]  
• Constantinescu, A., Wu, M., Asher, O., Diamond, I. (2004). cAMP-dependent Protein Kinase Type I Regulates Ethanol-induced cAMP Response Element-mediated Gene Expression via Activation of CREB-binding Protein and Inhibition of MAPK. J. Biol. Chem. 279: 43321-43329 [Abstract] [Full Text]  
• Boguslawski, G., McGlynn, P. W., Harvey, K. A., Kovala, A. T. (2004). SU1498, an Inhibitor of Vascular Endothelial Growth Factor Receptor 2, Causes Accumulation of Phosphorylated ERK Kinases and Inhibits Their Activity in Vivo and in Vitro. J. Biol. Chem. 279: 5716-5724 [Abstract] [Full Text]  
• Kang, M.-A., Yun, S.-Y., Won, J. (2003). Rosmarinic acid inhibits Ca2+-dependent pathways of T-cell antigen receptor-mediated signaling by inhibiting the PLC-gamma 1 and Itk activity. Blood 101: 3534-3542 [Abstract] [Full Text]  
• Maiyar, A. C., Leong, M. L.L., Firestone, G. L. (2003). Importin-alpha Mediates the Regulated Nuclear Targeting of Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by Recognition of a Nuclear Localization Signal in the Kinase Central Domain. Mol. Biol. Cell 14: 1221-1239 [Abstract] [Full Text]  
• Dash, R., Schmidt, A. G, Pathak, A., Gerst, M. J, Biniakiewicz, D., Kadambi, V. J, Hoit, B. D, Abraham, W. T, Kranias, E. G (2003). Differential regulation of p38 mitogen-activated protein kinase mediates gender-dependent catecholamine-induced hypertrophy. Cardiovasc Res 57: 704-714 [Abstract] [Full Text]  
• Cottom, J., Salvador, L. M., Maizels, E. T., Reierstad, S., Park, Y., Carr, D. W., Davare, M. A., Hell, J. W., Palmer, S. S., Dent, P., Kawakatsu, H., Ogata, M., Hunzicker-Dunn, M. (2003). Follicle-stimulating Hormone Activates Extracellular Signal-regulated Kinase but Not Extracellular Signal-regulated Kinase Kinase through a 100-kDa Phosphotyrosine Phosphatase. J. Biol. Chem. 278: 7167-7179 [Abstract] [Full Text]  
• Gomez, E., Pritchard, C., Herbert, T. P. (2002). cAMP-dependent Protein Kinase and Ca2+ Influx through L-type Voltage-gated Calcium Channels Mediate Raf-independent Activation of Extracellular Regulated Kinase in Response to Glucagon-like Peptide-1 in Pancreatic beta -Cells. J. Biol. Chem. 277: 48146-48151 [Abstract] [Full Text]  
• Gallagher, E. D., Xu, S., Moomaw, C., Slaughter, C. A., Cobb, M. H. (2002). Binding of JNK/SAPK to MEKK1 Is Regulated by Phosphorylation. J. Biol. Chem. 277: 45785-45792 [Abstract] [Full Text]  
• Nagarajan, U. M., Bushey, A., Boss, J. M. (2002). Modulation of Gene Expression by the MHC Class II Transactivator. J. Immunol. 169: 5078-5088 [Abstract] [Full Text]  
• Bjorndal, B., Helleland, C., Boe, S.-O., Gudbrandsen, O. A., Kalland, K.-H., Bohov, P., Berge, R. K., Lillehaug, J. R. (2002). Nuclear import of factors involved in signaling is inhibited in C3H/10T1/2 cells treated with tetradecylthioacetic acid. J. Lipid Res. 43: 1630-1640 [Abstract] [Full Text]  
• Buschbeck, M., Eickhoff, J., Sommer, M. N., Ullrich, A. (2002). Phosphotyrosine-specific Phosphatase PTP-SL Regulates the ERK5 Signaling Pathway. J. Biol. Chem. 277: 29503-29509 [Abstract] [Full Text]  
• Song, Z.-M., Undie, A. S., Koh, P. O., Fang, Y.-Y., Zhang, L., Dracheva, S., Sealfon, S. C., Lidow, M. S. (2002). D1 Dopamine Receptor Regulation of Microtubule-Associated Protein-2 Phosphorylation in Developing Cerebral Cortical Neurons. J. Neurosci. 22: 6092-6105 [Abstract] [Full Text]  
• Pursiheimo, J.-P., Saari, J., Jalkanen, M., Salmivirta, M. (2002). Cooperation of Protein Kinase A and Ras/ERK Signaling Pathways Is Required for AP-1-mediated Activation of Fibroblast Growth Factor-inducible Response Element (FiRE). J. Biol. Chem. 277: 25344-25355 [Abstract] [Full Text]  
• Nguyen, T.-H., Liu, J., Lombroso, P. J. (2002). Striatal Enriched Phosphatase 61 Dephosphorylates Fyn at Phosphotyrosine 420. J. Biol. Chem. 277: 24274-24279 [Abstract] [Full Text]  
• Whitehurst, A. W., Wilsbacher, J. L., You, Y., Luby-Phelps, K., Moore, M. S., Cobb, M. H. (2002). ERK2 enters the nucleus by a carrier-independent mechanism. Proc. Natl. Acad. Sci. USA 99: 7496-7501 [Abstract] [Full Text]  
• Winkler, A., Arkind, C., Mattison, C. P., Burkholder, A., Knoche, K., Ota, I. (2002). Heat Stress Activates the Yeast High-Osmolarity Glycerol Mitogen-Activated Protein Kinase Pathway, and Protein Tyrosine Phosphatases Are Essential under Heat Stress. Eukaryot Cell 1: 163-173 [Abstract] [Full Text]  
• Hanke, S., Nurnberg, B., Groll, D. H., Liebmann, C. (2001). Cross Talk between beta -Adrenergic and Bradykinin B2 Receptors Results in Cooperative Regulation of Cyclic AMP Accumulation and Mitogen-Activated Protein Kinase Activity. Mol. Cell. Biol. 21: 8452-8460 [Abstract] [Full Text]  
• Sanada, S., Kitakaze, M., Papst, P. J., Asanuma, H., Node, K., Takashima, S., Asakura, M., Ogita, H., Liao, Y., Sakata, Y., Ogai, A., Fukushima, T., Yamada, J., Shinozaki, Y., Kuzuya, T., Mori, H., Terada, N., Hori, M. (2001). Cardioprotective Effect Afforded by Transient Exposure to Phosphodiesterase III Inhibitors: The Role of Protein Kinase A and p38 Mitogen-Activated Protein Kinase. Circulation 104: 705-710 [Abstract] [Full Text]  
• Cha, H., Shapiro, P. (2001). Tyrosine-phosphorylated Extracellular Signal-regulated Kinase Associates with the Golgi Complex during G2/M Phase of the Cell Cycle: Evidence for Regulation of Golgi Structure. J. Cell Biol. 153: 1355-1368 [Abstract] [Full Text]  
• Aplin, A. E., Stewart, S. A., Assoian, R. K., Juliano, R.L. (2001). Integrin-mediated adhesion Regulates ERK Nuclear Translocation and Phosphorylation of Elk-1. J. Cell Biol. 153: 273-282 [Abstract] [Full Text]  
• Pearson, G., Robinson, F., Beers Gibson, T., Xu, B.-e, Karandikar, M., Berman, K., Cobb, M. H. (2001). Mitogen-Activated Protein (MAP) Kinase Pathways: Regulation and Physiological Functions. Endocr. Rev. 22: 153-183 [Abstract] [Full Text]  
• Kievit, P., Lauten, J. D., Maurer, R. A. (2001). Analysis of the Role of the Mitogen-Activated Protein Kinase in Mediating Cyclic-Adenosine 3',5'-Monophosphate Effects on Prolactin Promoter Activity. Mol. Endocrinol. 15: 614-624 [Abstract] [Full Text]  
• Puente, L. G., Stone, J. C., Ostergaard, H. L. (2000). Evidence for Protein Kinase C-Dependent and -Independent Activation of Mitogen-Activated Protein Kinase in T Cells: Potential Role of Additional Diacylglycerol Binding Proteins. J. Immunol. 165: 6865-6871 [Abstract] [Full Text]  
• Houslay, M. D., Kolch, W. (2000). Cell-Type Specific Integration of Cross-Talk between Extracellular Signal-Regulated Kinase and cAMP Signaling. Mol. Pharmacol. 58: 659-668 [Full Text]  
• Paul, S., Snyder, G. L., Yokakura, H., Picciotto, M. R., Nairn, A. C., Lombroso, P. J. (2000). The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway. J. Neurosci. 20: 5630-5638 [Abstract] [Full Text]  
• Camoretti-Mercado, B., Liu, H.-W., Halayko, A. J., Forsythe, S. M., Kyle, J. W., Li, B., Fu, Y., McConville, J., Kogut, P., Vieira, J. E., Patel, N. M., Hershenson, M. B., Fuchs, E., Sinha, S., Miano, J. M., Parmacek, M. S., Burkhardt, J. K., Solway, J. (2000). Physiological Control of Smooth Muscle-specific Gene Expression through Regulated Nuclear Translocation of Serum Response Factor. J. Biol. Chem. 275: 30387-30393 [Abstract] [Full Text]  
• Aimond, F., Rauzier, J.-M., Bony, C., Vassort, G. (2000). Simultaneous Activation of p38 MAPK and p42/44 MAPK by ATP Stimulates the K+ Current ITREK in Cardiomyocytes. J. Biol. Chem. 275: 39110-39116 [Abstract] [Full Text]  
• Tanoue, T., Yamamoto, T., Maeda, R., Nishida, E. (2001). A Novel MAPK Phosphatase MKP-7 Acts Preferentially on JNK/SAPK and p38alpha and beta MAPKs. J. Biol. Chem. 276: 26629-26639 [Abstract] [Full Text]  
• Tarrega, C., Blanco-Aparicio, C., Munoz, J. J., Pulido, R. (2002). Two Clusters of Residues at the Docking Groove of Mitogen-activated Protein Kinases Differentially Mediate Their Functional Interaction with the Tyrosine Phosphatases PTP-SL and STEP. J. Biol. Chem. 277: 2629-2636 [Abstract] [Full Text]  
• Cyert, M. S. (2001). Regulation of Nuclear Localization during Signaling. J. Biol. Chem. 276: 20805-20808 [Full Text]  
• Sohaskey, M. L., Ferrell, J. E. Jr. (2002). Activation of p42 Mitogen-activated Protein Kinase (MAPK), but not c-Jun NH2-Terminal Kinase, Induces Phosphorylation and Stabilization of MAPK Phosphatase XCL100 in Xenopus Oocytes. Mol. Biol. Cell 13: 454-468 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents