Cofilin activity during insulin-like growth factor I-stimulated neuroblastoma cell motility.
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.
Meyer
G
G
Department of Neurology, University of Michigan, 4414 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109, USA.
Kim
B
B
van Golen
C
C
Feldman
E L
EL
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
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
N Engl J Med. 2004 Sep 9;351(11):1097-105
15356307
Circulation. 1990 Feb;81(2 Suppl):III78-86
1967559
Heart. 2006 Sep;92 (9):1259-64
16488928
Am J Cardiol. 2000 Nov 15;86(10 ):1090-6
11074205
Am J Cardiol. 2001 Feb 15;87(4):413-9
11179524
Echocardiography. 2013 Aug;30(7):772-7
23432526
Am Heart J. 1991 Mar;121(3 Pt 1):864-71
2000754
Eur Heart J. 2007 Oct;28(20):2539-50
17428822
Herz. 2014 Mar;39(2):251-7
23649320
J Am Soc Echocardiogr. 2013 Dec;26(12 ):1424-33
24055123
J Am Soc Echocardiogr. 2011 Aug;24(8):898-908
21665431
J Am Coll Cardiol. 2003 Jan 15;41(2):217-23
12535812
Eur J Echocardiogr. 2006 Mar;7(2):79-108
16458610
J Am Soc Echocardiogr. 2011 Jun;24(6):651-62
21458230
Circ Cardiovasc Imaging. 2009 Jan;2(1):10-5
19808559
J Am Coll Cardiol. 2003 May 7;41(9):1510-8
12742291
Eur J Heart Fail. 2014 Oct;16(10):1096-103
25138249
Circulation. 2002 Mar 19;105(11):1387-93
11901053
N Engl J Med. 1985 Jan 31;312(5):277-83
2857050
N Engl J Med. 2006 Jul 20;355(3):251-9
16855265
Ann Intern Med. 2002 Oct 15;137(8):631-9
12379062