Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Pea15

  • Joanna E. Gawecka
  • Joe W. Ramos
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_212

Synonyms

Historical Background

Phosphoprotein Enriched in Astrocytes 15 kDa (PEA-15), also known as PED-15, is a 15 kDa protein that is highly expressed in the nervous system with particularly high levels in astrocytes and neurons of the hippocampus. Chneiweiss and colleagues first characterized PEA-15 as a major substrate for Protein Kinase C (PKC) in astrocytes and later cloned the cDNA encoding the protein (Araujo et al. 1993; Estelles et al. 1996). Subsequently, a portion of the 3′ UTR of the PEA-15 mRNA, called MAT1, was identified as a mammary transforming gene associated with mouse mammary carcinogenesis (Bera et al. 1994). It remains unclear how this relates to the function of the full-length PEA-15 protein. The initial functional significance of PEA-15 was identified when it was shown to be a phosphoprotein...

This is a preview of subscription content, log in to check access.

References

  1. Araujo H, Danziger N, Cordier J, Glowinski J, Chneiweiss H. Characterization of PEA-15, a major substrate for protein kinase C in astrocytes. J Biol Chem. 1993;268(8):5911–20.PubMedGoogle Scholar
  2. Bartholomeusz C, Itamochi H, Nitta M, Saya H, Ginsberg MH, Ueno NT. Antitumor effect of E1A in ovarian cancer by cytoplasmic sequestration of activated ERK by PEA15. Oncogene. 2006;25(1):79–90.PubMedGoogle Scholar
  3. Bartholomeusz C, Gonzalez-Angulo AM, Kazansky A, Krishnamurthy S, Liu P, Yuan LX, et al. PEA-15 inhibits tumorigenesis in an MDA-MB-468 triple-negative breast cancer xenograft model through increased cytoplasmic localization of activated extracellular signal-regulated kinase. Clin Cancer Res. 2010;16(6):1802–11.PubMedGoogle Scholar
  4. Bera TK, Guzman RC, Miyamoto S, Panda DK, Sasaki M, Hanyu K, et al. Identification of a mammary transforming gene (MAT1) associated with mouse mammary carcinogenesis. ProcNatlAcadSciUSA. 1994;91(21):9789–93.Google Scholar
  5. Condorelli G, Vigliotta G, Iavarone C, Caruso M, Tocchetti CG, Andreozzi F, et al. PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus. EMBO J. 1998;17(14):3858–66.PubMedGoogle Scholar
  6. Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalo P, Oriente F, et al. PED/PEA-15: an anti-apoptotic molecule that regulates FAS/TNFR1-induced apoptosis. Oncogene. 1999;18(31):4409–15.PubMedGoogle Scholar
  7. Estelles A, Yokoyama M, Nothias F, Vincent JD, Glowinski J, Vernier P, et al. The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs conserved on their full length in mouse and human. J Biol Chem. 1996;271(25):14800–6.PubMedGoogle Scholar
  8. Fiory F, Formisano P, Perruolo G, Beguinot F. Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism. Am J Physiol Endocrinol Metab. 2009;297(3):E592–601.PubMedGoogle Scholar
  9. Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B, et al. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase. Dev Cell. 2001;1(2):239–50.PubMedGoogle Scholar
  10. Glading A, Koziol JA, Krueger J, Ginsberg MH. PEA-15 inhibits tumor cell invasion by binding to extracellular signal-regulated kinase 1/2. Cancer Res. 2007;67(4):1536–44.PubMedGoogle Scholar
  11. Kitsberg D, Formstecher E, Fauquet M, Kubes M, Cordier J, Canton B, et al. Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis. J Neurosci. 1999;19(19):8244–51.PubMedGoogle Scholar
  12. Pastorino S, Renganathan H, Caliva MJ, Filbert EL, Opoku-Ansah J, Sulzmaier FJ, et al. The death effector domain protein PEA-15 negatively regulates T-cell receptor signaling. FASEB J. 2010;24(8):2818–28.Google Scholar
  13. Ramos JW. Cancer research center hotline: PEA-15 phosphoprotein: a potential cancer drug target. Hawaii MedJ. 2005;64(3):77–80.Google Scholar
  14. Ramos JW. The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells. Int J Biochem Cell Biol. 2008;40(12):2707–19.PubMedGoogle Scholar
  15. Ramos JW, Kojima TK, Hughes PE, Fenczik CA, Ginsberg MH. The death effector domain of PEA-15 is involved in its regulation of integrin activation. J Biol Chem. 1998;273(51):33897–900.PubMedGoogle Scholar
  16. Ramos JW, Townsend DA, Piarulli D, Kolata S, Light K, Hale G, et al. Deletion of PEA-15 in mice is associated with specific impairments of spatial learning abilities. BMC Neurosci. 2009;10:134.PubMedGoogle Scholar
  17. Renault-Mihara F, Beuvon F, Iturrioz X, Canton B, De BS, Leonard N, et al. Phosphoprotein enriched in astrocytes-15 kDa expression inhibits astrocyte migration by a protein kinase C delta-dependent mechanism. Mol Biol Cell. 2006;17(12):5141–52.PubMedGoogle Scholar
  18. Vaidyanathan H, Opoku-Ansah J, Pastorino S, Renganathan H, Matter ML, Ramos JW. ERK MAP kinase is targeted to RSK2 by the phosphoprotein PEA-15. Proc Natl Acad Sci USA. 2007;104(50):19837–42.PubMedGoogle Scholar
  19. Valmiki MG, Ramos JW. Death effector domain-containing proteins. Cell Mol Life Sci. 2009;66(5):814–30.PubMedGoogle Scholar
  20. Watanabe Y, Yamasaki F, Kajiwara Y, Saito T, Nishimoto T, Bartholomeusz C, et al. Expression of phosphoprotein enriched in astrocytes 15 kDa (PEA-15) in astrocytic tumors: a novel approach of correlating malignancy grade and prognosis. J Neurooncol. 2010;100(3):449–457.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.University of Hawai’i Cancer Center, University of Hawai’i at ManoaHonoluluUSA
  2. 2.The Cancer Research Center of HawaiiUniversity of HawaiiHonoluluUSA