1. Phospholipase C- I Is Required for Survival in Heat Stress: Involvement of Protein Kinase C-Depertment Bel-2 Phosphorylation
- Author
-
An-ling Liu, Qun-sheng Ji, Fan Deng, Zhi-peng Zou, Xiaochun Bai, Shen-qiu Luo, and Jie Bai
- Subjects
Phospholipase C ,Kinase ,Tyrosine phosphorylation ,General Medicine ,Biology ,Biochemistry ,Molecular biology ,Hsp70 ,chemistry.chemical_compound ,chemistry ,embryonic structures ,Phosphorylation ,Signal transduction ,Protein kinase A ,Molecular Biology ,Protein kinase C - Abstract
The consequences of heat-induced phospholipase C-gamma1 (PLC-gamma1) phosphorylation are not known. We investigated the role of PLC-gamma1 activation and its downstream targets during the cellular response to heat stress using mouse embryonic fibroblasts genetically deficient in PLC-gamma1 (Plcg1 null MEF) and its wild type (wt MEF) as models. Treatment of wt MEF with heat resulted in temperature- and heating duration-dependent tyrosine phosphorylation of PLC-gamma1. HSP70 synthesis and the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) and c-Jun N-terminal protein kinase (JNK) increased equally following heat treatment in both cell lines. However, heat-induced protein kinase C (PKC) activation was dramatically reduced in Plcg1 null MEF compared with wt MEF. Importantly, the mitochondrial localization of PKCalpha, PKC-dependent phosphorylation of Bcl-2, and cell viability in Plcg1 null MEF following heat treatment, were significantly decreased compared with the wild type. Furthermore, pretreatment with bryostatin-1, a PKC activator, enhanced Bcl-2 phosphorylation and cellular resistance to heat-induced apoptosis in Plcg1 null MEF. Taken together, these results suggest that PLC-gamma1 activation enhances cell survival through the PKC-dependent phosphorylation of Bcl-2 during the cellular response to heat stress.
- Published
- 2002