Abstract.
Insulin-like growth factor I (IGF-I) is a potent stimulator of neuroblastoma cell motility. Cell motility requires lamellipodium extension at the leading edge of the cell through organized actin polymerization, and IGF-I stimulates lamellipodial elaboration in human neuroblastoma cells. Rac is a Rho GTPase that stimulates lamellipodial formation via the regulation of actin polymerization. In this study, we show that IGF-I-stimulated phosphatidylinositol 3-kinase (PI-3K) activity promotes rac activation and subsequent activation of the down- stream effectors LIM kinase and cofilin. Overexpression of wild-type LIM kinase and wild-type Xenopus ADF/cofilin (XAC) suppresses IGF-I-stimulated motility in SH-SY5Y cells, while expression of dominant negative LIM kinase and constitutively active XAC increases SH-SY5Y motility in the absence of IGF-I stimulation. These results suggest that regulation by cofilin of actin depolymerization is important in the process of neuroblastoma cell motility, and IGF-I regulates cofilin activity in part through PI-3K, rac, and LIM kinase.
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Received 18 October 2004; received after revision 3 December 2004; accepted 16 December 2004
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Meyer, G., Kim, B., van Golen, C. et al. Cofilin activity during insulin-like growth factor I-stimulated neuroblastoma cell motility. CMLS, Cell. Mol. Life Sci. 62, 461–470 (2005). https://doi.org/10.1007/s00018-004-4456-6
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DOI: https://doi.org/10.1007/s00018-004-4456-6