Activation of P2Y2 receptors by UTP and ATP stimulates mitogen-activated kinase activity through a pathway that involves related adhesion focal tyrosine kinase and protein kinase C.

The Journal of Biological Chemistry
S P SoltoffL C Cantley

Abstract

We examined downstream signaling events that followed the exposure of PC12 cells to extracellular ATP and UTP, and we compared the effects of these P2 receptor agonists with those of growth factors and other stimuli. Based on early findings, we focused particular attention on the mitogen-activated protein (MAP) kinase pathway. ATP and/or UTP produced increases in tyrosine phosphorylation of multiple proteins, including p42 MAP (ERK2) kinase, related adhesion focal tyrosine kinase (RAFTK) (PYK2, CAKbeta), focal adhesion kinase (FAK), Shc, and protein kinase Cdelta (PKCdelta). MAP (ERK2) kinase activity (quantified by substrate phosphorylation) was increased by UTP, ATP, phorbol 12-myristate 13-acetate, ionomycin, and growth factors. UTP and ATP were equipotent (EC50 approximately 25 microM) in stimulating MAP kinase activity, suggesting that these effects were mediated via the Gi-linked P2Y2 (P2U) receptor. Consistent with this, the UTP- and ATP-promoted activation of MAP kinase was diminished in pertussis toxin-treated cells. Treatment of cells with pertussis toxin also reduced both the UTP-dependent increases in intracellular calcium ion concentration ([Ca2+]i) and the tyrosine phosphorylation of RAFTK. Similarly, when [Ca2+]i...Continue Reading

References

Sep 9, 1992·Biochimica Et Biophysica Acta·M A MajidY Kondo
Jun 11, 1992·Nature·R J EvansA Surprenant
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·N HuangL A Heppel
Jan 15, 1986·The Biochemical Journal·J L Gordon
May 1, 1995·Trends in Pharmacological Sciences·C Kennedy, P Leff
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K D LustigD Julius
Jan 1, 1994·Pharmacology & Therapeutics·M P Abbracchio, G Burnstock
Sep 1, 1993·The American Journal of Physiology·G R Dubyak, C el-Moatassim
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·L ErbG A Weisman
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M K NewellJ H Freed
Aug 31, 1993·Biochemical and Biophysical Research Communications·M A MajidY Kondo
Jul 1, 1996·The American Journal of Physiology·R K PalmerS K Fisher

❮ Previous
Next ❯

Citations

Feb 1, 2002·Biochemical and Biophysical Research Communications·Rosemary J KeoghCaroline P D Wheeler-Jones
May 12, 2006·Pflügers Archiv : European journal of physiology·Esmerilda G DelicadoJavier Gualix
Apr 6, 2006·Pflügers Archiv : European journal of physiology·Laurie ErbGary A Weisman
Apr 29, 2006·Pflügers Archiv : European journal of physiology·Heike FrankePeter Illes
Apr 12, 2008·Purinergic Signalling·John MeshkiSatya P Kunapuli
Apr 25, 2012·Purinergic Signalling·Gary A WeismanLaurie Erb
Apr 14, 2010·Molecular Neurobiology·Troy S PetersonGary A Weisman
Mar 8, 2000·Cellular Signalling·H AvrahamS Avraham
Aug 29, 2003·The Journal of Steroid Biochemistry and Molecular Biology·Parvaiz Q FarshoriKevin J Catt
May 23, 2001·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·S A Rooney
Mar 1, 2000·British Journal of Pharmacology·G LenzJ T Neary
Feb 9, 2002·British Journal of Pharmacology·Ursula UnterbergerStefan Boehm
Nov 9, 2002·Journal of Neurochemistry·Ana I JiménezM Teresa Miras-Portugal
Jun 8, 2013·Nucleosides, Nucleotides & Nucleic Acids·Ortal DaninoBilha Fischer
Oct 23, 2009·Molecular Biology of the Cell·Timothy J MyersSusan Wohler Sunnarborg
Apr 30, 2010·American Journal of Physiology. Cell Physiology·Ilene BoucherVickery Trinkaus-Randall
Apr 6, 2006·Biological & Pharmaceutical Bulletin·Katsutoshi MiyosawaNorimichi Nakahata
Aug 20, 2002·Japanese Journal of Pharmacology·Tomokazu WatanoJunko Kimura
May 10, 2001·Journal of Molecular and Cellular Cardiology·A L BayerA M Samarel
Apr 17, 2002·Neuropharmacology·S AmadioC Volonté
Aug 15, 2015·Molecular Reproduction and Development·Angélica S Martínez-Ramírez, Francisco G Vázquez-Cuevas

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.