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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2011.1
- 수록면
- 660 - 668 (9page)
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Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However,the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood.
Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress.
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참고문헌 (22)
참고문헌 신청
Allen JA / 2007 / Lipid raft microdomains and neurotransmitter signalling / Nat Rev Neurosci 8 : 128 ~ 140
Aoki Y / 2000 / Increased susceptibility to ischemia-induced brain damage in transgenic mice overexpressing a dominant negative form of SHP2 / Faseb J 14 : 1965 ~ 1973
Bennett AM / 1996 / Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression / Mol Cell Biol 16 : 1189 ~ 1202
Cameron PL / 1997 / Identification of caveolin and caveolin-related proteins in the brain / J Neurosci 17 : 9520 ~ 9535
Cao H / 2002 / A phosphotyrosinedependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase / J
Aoki Y / 2000 / Increased susceptibility to ischemia-induced brain damage in transgenic mice overexpressing a dominant negative form of SHP2 / Faseb J 14 : 1965 ~ 1973
Bennett AM / 1996 / Multiple requirements for SHPTP2 in epidermal growth factor-mediated cell cycle progression / Mol Cell Biol 16 : 1189 ~ 1202
Cameron PL / 1997 / Identification of caveolin and caveolin-related proteins in the brain / J Neurosci 17 : 9520 ~ 9535
Cao H / 2002 / A phosphotyrosinedependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: recruitment of C-terminal Src kinase / J
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