Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Signal Transduction*; Phosphoprotein Phosphatases/*metabolism ; Protein Serine-Threonine Kinases/*metabolism ; Receptors, Formyl Peptide/*metabolism; Amino Acid Motifs ; Animals ; Humans ; Phosphoprotein Phosphatases/chemistry ; Phosphorylation ; Protein Processing, Post-Translational ; Protein Serine-Threonine Kinases/chemistry

FPR1, FPR2, and FPR3 are members of Formyl Peptides Receptors (FPRs) family belonging to the GPCR superfamily. FPR2 is a low affinity receptor for formyl peptides and it is considered the most promiscuous member of this family. Intracellular signaling cascades triggered by FPRs include the activation of different protein kinases and phosphatase, as well as tyrosine kinase receptors transactivation. Protein kinases and phosphatases act coordinately and any impairment of their activation or regulation represents one of the most common causes of several human diseases. Several phospho-sites has been identified in protein kinases and phosphatases, whose role may be to expand the repertoire of molecular mechanisms of regulation or may be necessary for fine-tuning of switch properties. We previously performed a phospho-proteomic analysis in FPR2-stimulated cells that revealed, among other things, not yet identified phospho-sites on six protein kinases and one protein phosphatase. Herein, we discuss on the selective phosphorylation of Serine/Threonine-protein kinase N2, Serine/Threonine-protein kinase PRP4 homolog, Serine/Threonine-protein kinase MARK2, Serine/Threonine-protein kinase PAK4, Serine/Threonine-protein kinase 10, Dual specificity mitogen-activated protein kinase kinase 2, and Protein phosphatase 1 regulatory subunit 14A, triggered by FPR2 stimulation. We also describe the putative FPR2-dependent signaling cascades upstream to these specific phospho-sites.
Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Blood. 2017 Jan 12;129(2):e1-e12. (PMID: 28060719)
J Cell Biol. 2002 Jan 7;156(1):137-48. (PMID: 11777936)
Arch Biochem Biophys. 2016 Aug 1;603:10-9. (PMID: 27177968)
FASEB J. 1995 May;9(8):576-96. (PMID: 7768349)
Trends Cell Biol. 1997 Apr;7(4):162-7. (PMID: 17708935)
PLoS One. 2011;6(7):e21732. (PMID: 21754995)
Nat Cell Biol. 2016 Mar;18(3):303-10. (PMID: 26829388)
Cell Cycle. 2015;14(7):1059-69. (PMID: 25602630)
Biochem Biophys Res Commun. 2000 Aug 11;274(3):825-30. (PMID: 10924361)
Science. 2002 Dec 6;298(5600):1912-34. (PMID: 12471243)
Structure. 2007 Dec;15(12):1591-602. (PMID: 18073109)
Curr Opin Cell Biol. 2009 Apr;21(2):177-84. (PMID: 19208461)
Sci Rep. 2017 Feb 16;7:42575. (PMID: 28205613)
J Biol Chem. 2009 Dec 18;284(51):35273-7. (PMID: 19846560)
Science. 2015 Nov 20;350(6263):972-8. (PMID: 26516201)
Eur J Drug Metab Pharmacokinet. 2018 Aug;43(4):373-382. (PMID: 29488172)
J Smooth Muscle Res. 2017;53(0):1-19. (PMID: 28260704)
FASEB J. 2020 May;34(5):6920-6933. (PMID: 32239559)
Nat Struct Mol Biol. 2004 Dec;11(12):1192-7. (PMID: 15543157)
J Biol Chem. 2001 Jun 1;276(22):19588-96. (PMID: 11376011)
Free Radic Biol Med. 2004 Jan 15;36(2):189-200. (PMID: 14744631)
Biochem Biophys Res Commun. 2000 May 10;271(2):456-63. (PMID: 10799319)
Sci Signal. 2010 Jan 12;3(104):ra3. (PMID: 20068231)
Cell. 1997 Apr 18;89(2):297-308. (PMID: 9108484)
Gene. 2017 Mar 20;605:20-31. (PMID: 28007610)
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5680-5. (PMID: 17372192)
Biochem Pharmacol. 2018 Feb;148:27-40. (PMID: 29175420)
Nat Struct Mol Biol. 2010 Feb;17(2):216-21. (PMID: 20118938)
Cell Cycle. 2007 Aug 15;6(16):1966-9. (PMID: 17721078)
Nat Rev Mol Cell Biol. 2003 Aug;4(8):651-7. (PMID: 12923527)
Oncogene. 2014 Jun 19;33(25):3277-87. (PMID: 23893240)
Immunogenetics. 1999 May;49(5):369-75. (PMID: 10199912)
Nature. 2016 May 25;534(7605):55-62. (PMID: 27251275)
Biochemistry. 2009 Mar 31;48(12):2661-74. (PMID: 19161339)
Mol Biol Cell. 2005 Oct;16(10):4572-83. (PMID: 16079174)
Sci Rep. 2019 Nov 29;9(1):17894. (PMID: 31784636)
Arch Biochem Biophys. 2007 Mar 15;459(2):288-94. (PMID: 17166481)
Dev Cell. 2010 Dec 14;19(6):845-57. (PMID: 21145500)
Anticancer Res. 2015 May;35(5):2769-74. (PMID: 25964556)
Mol Cell. 2008 Aug 8;31(3):438-48. (PMID: 18691976)
Sci Rep. 2017 Jun 9;7(1):3153. (PMID: 28600569)
J Mol Biol. 2001 Dec 7;314(4):839-49. (PMID: 11734001)
Nat Immunol. 2006 Nov;7(11):1143-9. (PMID: 17053799)
J Biol Chem. 2001 Aug 3;276(31):29072-8. (PMID: 11397799)
J Biol Chem. 1997 Jan 10;272(2):937-44. (PMID: 8995385)
Cell Signal. 2008 Jul;20(7):1320-8. (PMID: 18424072)
EMBO J. 2004 Feb 25;23(4):833-43. (PMID: 14976552)
Cancer Discov. 2015 Nov;5(11):1194-209. (PMID: 26293922)
J Biol Chem. 2004 Nov 12;279(46):48319-28. (PMID: 15319445)
Neural Regen Res. 2020 Jul;15(7):1191-1198. (PMID: 31960798)
J Cardiovasc Pharmacol. 2017 Sep;70(3):142-158. (PMID: 28328745)
Mol Cell Biol. 2001 May;21(9):3206-19. (PMID: 11287624)
Cell. 2000 May 12;101(4):345-8. (PMID: 10830161)
Circ Res. 2007 Jan 5;100(1):121-9. (PMID: 17158339)
PLoS Genet. 2014 Jan;10(1):e1004062. (PMID: 24465218)
Proc Natl Acad Sci U S A. 2010 Jan 26;107(4):1660-5. (PMID: 20080636)
Eur J Biochem. 1995 Jan 15;227(1-2):344-51. (PMID: 7851406)
IUBMB Life. 2012 Sep;64(9):732-9. (PMID: 22815089)
EMBO J. 2003 Sep 1;22(17):4431-42. (PMID: 12941695)
Cardiovasc Res. 2006 Feb 1;69(2):491-501. (PMID: 16336954)
Sci China Life Sci. 2011 Apr;54(4):336-41. (PMID: 21509657)
World J Gastroenterol. 2016 Jan 21;22(3):1224-35. (PMID: 26811660)
J Biol Chem. 1996 Nov 15;271(46):28772-6. (PMID: 8910519)
Trends Cell Biol. 2001 May;11(5):220-30. (PMID: 11316611)
J Biol Chem. 1997 Nov 21;272(47):29449-53. (PMID: 9368003)
Chem Rev. 2001 Aug;101(8):2353-64. (PMID: 11749377)
Cell Signal. 2007 Sep;19(9):1939-48. (PMID: 17594911)
Nucleic Acids Res. 2012 Jan;40(Database issue):D261-70. (PMID: 22135298)
Nat Rev Clin Oncol. 2014 Jul;11(7):385-400. (PMID: 24840079)
Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18378-83. (PMID: 19011111)
Am J Physiol Regul Integr Comp Physiol. 2014 Aug 1;307(3):R256-70. (PMID: 24898838)
Molecules. 2017 Mar 13;22(3):. (PMID: 28335409)
Mol Cell. 2009 Jan 30;33(2):237-47. (PMID: 19187764)
Mol Cell Biol. 2009 Jun;29(11):3018-32. (PMID: 19289496)
Am J Respir Cell Mol Biol. 2008 Dec;39(6):638-43. (PMID: 18757304)
Am J Physiol Cell Physiol. 2012 Jul 1;303(1):C58-68. (PMID: 22538237)
J Proteome Res. 2008 Dec;7(12):5167-76. (PMID: 19367720)
Biochem Biophys Res Commun. 2003 Mar 7;302(2):186-92. (PMID: 12604330)
J Biol Chem. 1997 Sep 5;272(36):22679-84. (PMID: 9278426)
J Biol Chem. 2011 Apr 1;286(13):10998-1002. (PMID: 21310961)
Curr Opin Cell Biol. 1997 Apr;9(2):180-6. (PMID: 9069255)
J Biol Chem. 2016 May 6;291(19):10148-61. (PMID: 26945071)
J Clin Invest. 1990 Mar;85(3):714-21. (PMID: 2155923)
Mol Reprod Dev. 1995 Dec;42(4):459-67. (PMID: 8607977)
J Clin Invest. 2006 Jul;116(7):1776-83. (PMID: 16823475)
Oncogene. 2002 May 30;21(24):3939-48. (PMID: 12032833)
Nat Commun. 2020 Feb 14;11(1):885. (PMID: 32060286)
Trends Immunol. 2018 Oct;39(10):815-829. (PMID: 30195466)
EMBO J. 1995 Jul 3;14(13):3136-45. (PMID: 7542586)
Inflamm Res. 2018 Aug;67(8):711-722. (PMID: 29922854)
Cell Signal. 2007 Oct;19(10):2106-17. (PMID: 17643960)
Mol Cell Biol. 2002 Jan;22(2):567-77. (PMID: 11756552)
Cell Signal. 2006 Sep;18(9):1473-81. (PMID: 16427251)
Mol Biol Cell. 2005 Sep;16(9):4410-22. (PMID: 16014608)
Mol Cell Proteomics. 2009 Jul;8(7):1751-64. (PMID: 19369195)
FEBS Lett. 2001 Mar 30;493(2-3):91-4. (PMID: 11287002)
J Biol Chem. 2001 Aug 24;276(34):32115-21. (PMID: 11413130)
Pediatr Pulmonol. 2005 Nov;40(5):398-407. (PMID: 16130142)
BMC Cancer. 2014 Dec 16;14:961. (PMID: 25510623)
Mol Cell Proteomics. 2014 Jul;13(7):1690-704. (PMID: 24719451)
J Biol Chem. 2003 May 16;278(20):18221-8. (PMID: 12639966)
J Clin Invest. 2013 Jan;123(1):443-54. (PMID: 23241962)
J Exp Clin Cancer Res. 2019 Apr 18;38(1):170. (PMID: 30999932)
J Cell Biochem. 2010 Aug 1;110(5):1244-54. (PMID: 20564219)
J Neurochem. 2007 Nov;103(4):1553-66. (PMID: 17727628)
J Cell Sci. 2003 Sep 1;116(Pt 17):3471-8. (PMID: 12893811)
Mol Cell. 2009 Jul 10;35(1):1-10. (PMID: 19595711)
J Biochem. 2003 Jan;133(1):17-27. (PMID: 12761194)
Nature. 2002 Jun 27;417(6892):949-54. (PMID: 12068308)
J Biochem. 2019 Apr 1;165(4):301-307. (PMID: 30590682)
J Biol Chem. 2000 Apr 7;275(14):9897-900. (PMID: 10744661)
Biochem Biophys Res Commun. 2013 Apr 26;434(1):137-42. (PMID: 23541585)
Neurobiol Aging. 2018 Aug;68:123-133. (PMID: 29602494)
Biochem Biophys Res Commun. 2002 Oct 4;297(4):773-8. (PMID: 12359219)
J Biol Chem. 1996 Aug 30;271(35):21005-1011. (PMID: 8702863)
J Cell Sci. 2018 Oct 17;131(20):. (PMID: 30333133)
Biochem Biophys Res Commun. 1994 Mar 15;199(2):897-904. (PMID: 8135837)
Cell Growth Differ. 1993 Nov;4(11):921-9. (PMID: 8297798)
Mol Cancer. 2010 Aug 18;9:218. (PMID: 20718987)
Curr Neuropharmacol. 2014 May;12(3):213-8. (PMID: 24851086)
Biochem Biophys Res Commun. 2004 Mar 26;316(1):39-47. (PMID: 15003508)
Biochem Biophys Res Commun. 1999 Dec 20;266(2):291-5. (PMID: 10600495)
Br J Pharmacol. 2016 Feb;173(4):635-48. (PMID: 26013585)
Cell Signal. 2011 Dec;23(12):1961-71. (PMID: 21777671)
Free Radic Biol Med. 2011 Sep 15;51(6):1126-36. (PMID: 21708247)
Small GTPases. 2014;5:. (PMID: 24658305)
Cell Tissue Res. 2018 Mar;371(3):425-436. (PMID: 29350282)
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3603-8. (PMID: 11904423)
Nucleic Acids Res. 1997 Mar 1;25(5):1028-35. (PMID: 9102632)
Biol Cell. 2008 Feb;100(2):97-108. (PMID: 18199048)
J Biol Chem. 2011 Nov 4;286(44):38448-55. (PMID: 21921027)
J Biol Chem. 2009 Aug 28;284(35):23225-33. (PMID: 19574224)
FEBS Lett. 1995 Dec 4;376(3):172-6. (PMID: 7498535)
Neurochem Res. 2010 Dec;35(12):2018-26. (PMID: 21042851)
Mol Cancer Res. 2009 Jun;7(6):907-15. (PMID: 19491199)
J Biol Chem. 1994 Mar 18;269(11):7851-4. (PMID: 8132501)
FEBS Lett. 2000 Jun 23;475(3):197-200. (PMID: 10869555)
Biochemistry. 2013 Dec 17;52(50):9068-79. (PMID: 24251416)
Arch Biochem Biophys. 2009 Jan 1;481(1):94-100. (PMID: 18996352)
Dev Biol. 1999 Oct 1;214(1):87-101. (PMID: 10491259)
FEBS Lett. 2013 May 21;587(10):1536-42. (PMID: 23583448)
Curr Biol. 2004 Aug 24;14(16):1425-35. (PMID: 15324659)
Biochem Pharmacol. 2011 Nov 1;82(9):1145-52. (PMID: 21784060)
Mol Cell Biol. 2006 Oct;26(19):7086-102. (PMID: 16980613)
PLoS One. 2019 Jun 6;14(6):e0217815. (PMID: 31170199)
Nature. 2006 Aug 3;442(7102):576-9. (PMID: 16885985)
J Proteomics. 2014 Jan 16;96:253-62. (PMID: 24275569)
Biochem J. 2010 Jan 15;425(3):465-73. (PMID: 20070256)
Curr Opin Cell Biol. 2009 Apr;21(2):185-93. (PMID: 19216065)
Trends Plant Sci. 2015 May;20(5):269-272. (PMID: 25795237)
Cancer Res. 2016 Jun 1;76(11):3122-6. (PMID: 27197163)
Trends Biochem Sci. 2002 Dec;27(12):619-27. (PMID: 12468231)
J Biol Chem. 2008 Jul 4;283(27):18873-82. (PMID: 18424437)
EMBO J. 2008 Feb 20;27(4):704-14. (PMID: 18239682)
Oncol Rep. 2017 Dec;38(6):3297-3308. (PMID: 29039544)
Mol Oncol. 2012 Jun;6(3):284-98. (PMID: 22217540)
J Biol Chem. 2010 Jul 30;285(31):23699-710. (PMID: 20507994)
J Biochem. 1995 Dec;118(6):1104-7. (PMID: 8720121)
Oxid Med Cell Longev. 2019 Dec 2;2019:2051235. (PMID: 31871542)
Mol Cell Biol. 1992 Dec;12(12):5824-33. (PMID: 1333047)
EMBO J. 2007 May 2;26(9):2251-61. (PMID: 17446865)
Cell. 2006 Nov 3;127(3):635-48. (PMID: 17081983)
Mol Pharmacol. 2005 Jul;68(1):145-51. (PMID: 15814573)
Elife. 2017 Apr 21;6:. (PMID: 28430576)
Nat Biotechnol. 2006 Oct;24(10):1285-92. (PMID: 16964243)
J Proteome Res. 2013 Jan 4;12(1):260-71. (PMID: 23186163)
Am J Physiol Renal Physiol. 2006 Mar;290(3):F650-6. (PMID: 16204412)
FASEB J. 2020 Feb;34(2):1958-1969. (PMID: 31907980)
J Biol Chem. 1997 Jul 4;272(27):17204-8. (PMID: 9202043)
J Cell Sci. 2002 Oct 15;115(Pt 20):3947-56. (PMID: 12244132)
Mol Cells. 2013 Jun;35(6):526-32. (PMID: 23686430)
Free Radic Biol Med. 2009 Oct 1;47(7):983-91. (PMID: 19596065)
Nature. 1994 Jun 2;369(6479):411-4. (PMID: 8196769)
Curr Biol. 2004 Apr 20;14(8):736-41. (PMID: 15084291)
EMBO J. 2003 Oct 1;22(19):5090-101. (PMID: 14517247)
J Cell Sci. 2005 May 1;118(Pt 9):1861-72. (PMID: 15827085)
Sci Signal. 2009 Aug 18;2(84):ra46. (PMID: 19690332)
Trends Cell Biol. 2005 Mar;15(3):163-71. (PMID: 15752980)
Bioessays. 1996 Jul;18(7):567-77. (PMID: 8757935)
Neuron. 2002 Dec 19;36(6):1145-58. (PMID: 12495628)
J Physiol. 2013 Jun 15;591(12):2971-86. (PMID: 23613531)
FASEB J. 2010 Jun;24(6):1637-48. (PMID: 20071654)
J Hypertens. 2005 Jun;23(6):1183-90. (PMID: 15894894)
J Mol Med (Berl). 2013 Jul;91(7):781-9. (PMID: 23404331)
FEBS Lett. 1997 Jun 30;410(2-3):356-60. (PMID: 9237662)
Structure. 1994 May 15;2(5):345-55. (PMID: 8081750)
Mol Cell Biol. 2010 Nov;30(21):5043-56. (PMID: 20733003)
Int J Mol Sci. 2018 Apr 16;19(4):. (PMID: 29659553)
Biochim Biophys Acta. 2012 Feb;1823(2):465-75. (PMID: 22173096)
J Biol Chem. 2001 Aug 24;276(34):32247-56. (PMID: 11418604)
Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. (PMID: 16175573)
J Immunol. 2007 Dec 15;179(12):8112-21. (PMID: 18056353)
Int J Mol Sci. 2013 Apr 02;14(4):7193-230. (PMID: 23549262)
EMBO Mol Med. 2016 Jan 15;8(3):232-46. (PMID: 26772600)
Sci Rep. 2017 Mar 16;7(1):206. (PMID: 28303030)
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. (PMID: 18669648)
J Cell Biol. 2002 Sep 30;158(7):1287-97. (PMID: 12356872)
EMBO J. 1992 Dec;11(13):4815-24. (PMID: 1464311)
Arch Biochem Biophys. 2008 Nov 15;479(2):170-8. (PMID: 18835241)
Biochem J. 2006 May 15;396(1):193-200. (PMID: 16472257)
Physiol Rev. 2015 Jul;95(3):995-1024. (PMID: 26133936)
J Biochem. 1999 Sep;126(3):475-84. (PMID: 10467162)
J Cell Mol Med. 2019 Mar;23(3):2251-2255. (PMID: 30636369)
J Neurosci. 2007 Apr 18;27(16):4413-23. (PMID: 17442826)
Mol Cell Biol. 2011 Jan;31(1):81-91. (PMID: 20974804)
Database (Oxford). 2014 Feb 05;2014:bat085. (PMID: 24501395)
J Biol Chem. 2000 Nov 3;275(44):34451-8. (PMID: 10926925)
Oncogene. 2014 Jun 26;33(26):3473-84. (PMID: 23934187)
Biochemistry. 2003 Apr 22;42(15):4520-6. (PMID: 12693948)
BMC Cancer. 2016 Jul 18;16:490. (PMID: 27432059)
J Biol Chem. 2000 Apr 14;275(15):11064-70. (PMID: 10753910)
J Immunol. 2005 Aug 1;175(3):1843-50. (PMID: 16034127)
Antiinflamm Antiallergy Agents Med Chem. 2012;11(1):20-36. (PMID: 22934745)
J Proteome Res. 2008 Feb;7(2):526-34. (PMID: 18088087)
EMBO J. 1998 Nov 16;17(22):6527-40. (PMID: 9822598)
J Cell Biol. 2012 Dec 10;199(6):969-84. (PMID: 23209304)
J Biol Chem. 2003 Dec 5;278(49):48794-804. (PMID: 14512413)
Oncotarget. 2017 Feb 21;8(8):14173-14191. (PMID: 27845911)
J Biol Chem. 2012 Jun 8;287(24):20590-602. (PMID: 22511787)
Enzyme Res. 2011;2011:329098. (PMID: 21904669)
FEBS J. 2015 Dec;282(24):4658-71. (PMID: 26426570)
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4262-5. (PMID: 11917128)
Oncogene. 2005 Mar 3;24(10):1653-62. (PMID: 15744326)
J Immunol. 1995 Mar 1;154(5):2413-22. (PMID: 7868907)
J Biol Chem. 2003 Dec 12;278(50):50578-87. (PMID: 14514689)
Prostate. 2017 Nov;77(15):1452-1467. (PMID: 28875501)
Neurobiol Aging. 2008 Feb;29(2):231-40. (PMID: 17196307)
Cell. 1995 Jan 27;80(2):187-97. (PMID: 7834739)
J Biol Chem. 1995 Mar 24;270(12):6729-33. (PMID: 7896817)
Mol Cell Biol. 1997 Apr;17(4):2247-56. (PMID: 9121475)
Biochem J. 2011 Sep 15;438(3):535-43. (PMID: 21749319)
Sci Signal. 2011 Mar 15;4(164):rs3. (PMID: 21406692)
Neoplasma. 2019 Sep;66(5):785-791. (PMID: 31288528)
Int J Mol Sci. 2014 Oct 29;15(11):19700-28. (PMID: 25356505)
J Proteome Res. 2013 Apr 5;12(4):1856-67. (PMID: 23438512)
EMBO J. 2000 Feb 15;19(4):496-503. (PMID: 10675318)
Eur J Pharmacol. 2013 Feb 15;701(1-3):96-105. (PMID: 23348708)
Cell Motil Cytoskeleton. 2008 Sep;65(9):687-707. (PMID: 18615630)
Oxid Med Cell Longev. 2018 Mar 18;2018:2609847. (PMID: 29743977)
Am J Cancer Res. 2016 Nov 01;6(11):2599-2610. (PMID: 27904774)
Oncol Rep. 2013 Oct;30(4):1542-8. (PMID: 23842845)

CUP B61C17000070007 - SURF 17061BP000000002 Sviluppo di Approcci Terapeutici INnovativi per patologie neoplastiche resistenti ai trattamenti (SATIN)

Keywords: FPR2; MAP2K2; MARK2; PAK4; PKN2; PPP1R14A.; PRP4; STK10; cell signaling; phospho-sites

0 (Receptors, Formyl Peptide)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 3.1.3.16 (Phosphoprotein Phosphatases)

Date Created: 20200531 Date Completed: 20210216 Latest Revision: 20211204

20231215

PMC7312799

10.3390/ijms21113818

32471307