Cross-Talk in Nucleotide Signaling in Glioma C6 Cells

  • Dorota Wypych
  • Jolanta BarańskaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1202)


The chapter is focused on the mechanism of action of metabotropic P2Y nucleotide receptors: P2Y1, P2Y2, P2Y12, P2Y14 and the ionotropic P2X7 receptor in glioma C6 cells. P2Y1 and P2Y12 both respond to ADP, but while P2Y1 links to PLC and elevates cytosolic Ca2+ concentration, P2Y12 negatively couples to adenylate cyclase, maintaining cAMP at low level. In glioma C6, these two P2Y receptors modulate activities of ERK1/2 and PI3K/Akt signaling and the effects depend on physiological conditions of the cells. During prolonged serum deprivation, cell growth is arrested, the expression of the P2Y1 receptor strongly decreases and P2Y12 becomes a major player responsible for ADP-evoked signal transduction. The P2Y12 receptor activates ERK1/2 kinase phosphorylation (a known cell proliferation regulator) and stimulates Akt activity, contributing to glioma invasiveness. In contrast, P2Y1 has an inhibitory effect on Akt pathway signaling. Furthermore, the P2X7 receptor, often responsible for apoptotic fate, is not involved in Ca2+elevation in C6 cells. The shift in nucleotide receptor expression from P2Y1 to P2Y12 during serum withdrawal, the cross talk between both receptors and the lack of P2X7 activity shows the precise self-regulating mechanism, enhancing survival and preserving the neoplastic features of C6 cells.


P2Y1, P2Y2, P2Y12, P2Y14, P2X7 nucleotide receptors Serum withdrawal P2Y1/P2Y12 cross-talk cAMP ERK1/2 PI3K/Akt activity Glioma C6 cells 



protein kinase B/Akt kinase




2’,3′- 0-(4-benzoylbenzoyl)-ATP


intracellular calcium concentration




endoplasmic reticulum


extracellular signal-regulated kinases 1/2.


GTP-ase activating protein 1


glioblastoma multiforme


guanine nucleotide exchange factor


glial fibrillary acidic protein


green fluorescent protein


protein-coupled receptor






MAP kinase-ERK kinase


2-methylthio ADP


periodate-oxidized ATP


phosphoinositide-dependent protein kinase 1.


phosphatidylinositol 3-kinase




protein kinase A


protein kinase C


phospholipase C


pyridoxal-phosphate-6-azophenyl-2,4disulfonic acid


phosphatase and tensin homolog


pertussis toxin


receptor tyrosine kinase


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Nencki Institute of Experimental BiologyPolish Academy of SciencesWarsawPoland

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