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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 335 - 344 (10page)
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초록· 키워드
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Rat pheochromocytoma (PC12) cells have been used to investigate neurite outgrowth. Nerve growth factor (NGF) has been well known to induce neurite outgrowth from PC12 cells. RhoA belongs to Ras-related small GTP-binding proteins, which regulate a variety of cellular processes, including cell morphology alteration,actin dynamics, and cell migration. NGF suppressed GTP-RhoA levels after 12 h in PC12 cells and was consistently required for a long time to induce neurite outgrowth. Constitutively active (CA)-RhoA suppressed neurite outgrowth from PC12 cells in response to NGF, whereas dominant-negative (DN)-RhoA stimulated it, suggesting that RhoA inactivation is essential for neurite outgrowth. Here, we investigated the mechanism of RhoA inactivation. DN-p190RhoGAP abrogated neurite outgrowth, whereas wild-type (WT)-p190RhoGAP and WT-Src synergistically stimulated it along with accelerating RhoA inactivation, suggesting that p190RhoGAP, which can be activated by Src, is a major component in inhibiting RhoA in response to NGF in PC12 cells. Contrary to RhoA, Rap1was activated by NGF, and DN-Rap1 suppressed neurite outgrowth, suggesting that Rap1 is also essential for neurite outgrowth. RhoA was co-immunoprecipitated with Rap1, suggesting that Rap1 interacts with RhoA. Furthermore, a DN-Rap-dependent RhoGAP (ARAP3) prevented RhoA inactivation, abolishing neurite formation from PC12 cells in response to NGF. These results suggest that NGF activates Rap1, which, in turn, up-regulates ARAP3 leading to RhoA inactivation and neurite outgrowth from PC12cells. Taken together, p190RhoGAP and ARAP3 seem to be two main factors inhibiting RhoA activity during neurite outgrowth in PC12 cells in response to NGF.
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참고문헌 (21)
참고문헌 신청
Aoki K / 2005 / Local phosphatidylinositol 3,4,5-trisphosphate accumulation recruits Vav2 and Vav3 to activate Rac1/Cdc42 and initiate neurite outgrowth in nerve growth facto
Billuart P / 2001 / Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway / Cell 107 : 195 ~ 207
Bishop AL / 2000 / Rho GTPases and their effector proteins / Biochem J 348 : 241 ~ 255
Bos JL / 2003 / The role of Rap1 in integrin-mediated cell adhesion / Biochem Soc Trans 31 : 83 ~ 86
Brouns MR / 2000 / The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development / Development 127 : 4891 ~ 4903
Billuart P / 2001 / Regulating axon branch stability: the role of p190 RhoGAP in repressing a retraction signaling pathway / Cell 107 : 195 ~ 207
Bishop AL / 2000 / Rho GTPases and their effector proteins / Biochem J 348 : 241 ~ 255
Bos JL / 2003 / The role of Rap1 in integrin-mediated cell adhesion / Biochem Soc Trans 31 : 83 ~ 86
Brouns MR / 2000 / The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development / Development 127 : 4891 ~ 4903
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