title: Cofilin activity during insulin-like growth factor I-stimulated neuroblastoma cell motility.
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.
authors.affiliation: Department of Neurology, University of Michigan, 4414 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
authors.forename: G
authors.initials: G
authors.lastname: Meyer
authors.forename: B
authors.initials: B
authors.lastname: Kim
authors.forename: C
authors.initials: C
authors.lastname: van Golen
authors.forename: E L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D051339:Actin Depolymerizing Factors; D000199:Actins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology / Q000502:physiology*; D054461:Lim Kinases; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology; D014981:Xenopus; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D007334:Insulin-Like Growth Factor I; D011494:Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; C515892:LIMK1 protein, human; D054461:Lim Kinases; D020744:rac GTP-Binding Proteins
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