Src homology domains of phospholipase C γ1 inhibit nerve growth factor- induced differentiation of PC12 cells

Sun Sik Bae, Young Han Lee, Jong Soo Chang, Sehamuddin H. Galadari, Yong Sik Kim, Sung Ho Ryu, Pann Ghill Suh

Research output: Contribution to journalArticle

Abstract

Phospholipase C γ1 (PLC-γ1) is phosphorylated on treatment of cells with nerve growth factor (NGF). To assess the role of PLC-γ1 in mediating the neuronal differentiation induced by NGF treatment, we established PC12 cells that overexpress whole PLC- γ1 (PLC-γ1PC12), the SH2-SH2-SH3 domain (PLC-γ1SH223PC12), SH2-SH2-deleted mutants (PLC-γ1ΔSH22PC12), and SH3- deleted mutants (PLC-γ1ΔSH3PC12). Overexpressed whole PLC-γ1 or the SH2- SH2-SH3 domain of PLC-γ1 stimulated cell growth and inhibited NGF-induced neurite outgrowth of PC12 cells. However, cells expressing PLC-γ1 lacking the SH2-SH2 domain or the SH3 domain had no effect on NGF-induced neuronal differentiation. Overexpression of intact PLC-γ1 resulted in a threefold increase in total inositol phosphate accumulation on treatment with NGF. However, overexpression of the SH2-SH2-SH3 domain of PLC-γ1 did not alter total inositol phosphate accumulation. To investigate whether the SH2-SH2- SH3 domain of PLC-γ1 can mediate the NGF-induced signal, tyrosine phosphorylation of the SH2-SH2-SH3 domain of PLC-γ1 on NGF treatment was examined. The SH2-SH2-SH3 domain of PLC-γ1 as well as intact PLC-γ1 could be tyrosine-phosphorylated on NGF treatment. These results indicate that the overexpressed SH2-SH2-SH3 domain of PLC-γ1 can block the differentiation of PC12 cells induced by NGF and that the inhibition appears not to be related to the lipase activity of PLC-γ1 but to the SH2-SH2-SH3 domain of PLC-γ1.

Original languageEnglish (US)
Pages (from-to)178-185
Number of pages8
JournalJournal of Neurochemistry
Volume71
Issue number1
DOIs
StatePublished - Jul 1998

Keywords

  • Differentiation
  • Nerve growth factor
  • PC12 cells
  • Phospholipase C γ1
  • Proliferation
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Src homology domains of phospholipase C γ1 inhibit nerve growth factor- induced differentiation of PC12 cells'. Together they form a unique fingerprint.

  • Cite this