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PMID: 9490736 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Integrin alphavbeta3 requirement for sustained mitogen-activated protein kinase activity during angiogenesis.

The Journal of cell biology ·Vol. 140 ·No. 5 ·1998-03-09 ·Pages 1255-63

Eliceiri BP, Klemke R, Strömblad S, Cheresh DA

Abstract

Angiogenesis depends on growth factors and vascular cell adhesion events. Integrins and growth factors are capable of activating the ras/MAP kinase pathway in vitro, yet how these signals influence endothelial cells during angiogenesis is unknown. Upon initiation of angiogenesis with basic fibroblast growth factor (bFGF) on the chick chorioallantoic membrane (CAM), endothelial cell mitogen-activated protein (MAP) kinase (ERK) activity was detected as early as 5 min yet was sustained for at least 20 h. The initial wave of ERK activity (5-120 min) was refractory to integrin antagonists, whereas the sustained activity (4-20 h) depended on integrin alphavbeta3, but not beta1 integrins. Inhibition of MAP kinase kinase (MEK) during this sustained alphavbeta3-dependent ERK signal blocked the formation of new blood vessels while not influencing preexisting blood vessels on the CAM. Inhibition of MEK also blocked growth factor induced migration but not adhesion of endothelial cells in vitro. Therefore, angiogenesis depends on sustained ERK activity regulated by the ligation state of both a growth factor receptor and integrin alphavbeta3.

MeSH Terms
Animals Blood Vessels/embryology Calcium-Calmodulin-Dependent Protein Kinases/metabolism Cell Line Cell Movement Chick Embryo Chorion Endothelium/cytology Enzyme Induction Fluorescent Antibody Technique, Indirect Humans Kinetics Neovascularization, Physiologic/physiology Phosphorylation Rabbits Receptors, Vitronectin/metabolism
Chemicals
Receptors, Vitronectin Calcium-Calmodulin-Dependent Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Eliceiri B P
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Klemke R
Strömblad S
Cheresh D A
References (45)
45 references, click to expand
  1. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.
    Science. 1995 Nov 24;270(5240):1326-31 PMID: 7481820
  2. Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin.
    J Clin Invest. 1995 Oct;96(4):1815-22 PMID: 7560073
  3. Transient functional expression of alphaVbeta 3 on vascular cells during wound repair.
    Am J Pathol. 1996 May;148(5):1407-21 PMID: 8623913
  4. Thrombin receptor activation elicits rapid protein tyrosine phosphorylation and stimulation of the raf-1/MAP kinase pathway preceding delayed mitogenesis in cultured rat aortic smooth muscle cells: evidence for an obligate autocrine mechanism promoting cell proliferation induced by G-protein-coupled receptor agonist.
    J Clin Invest. 1996 Mar 1;97(5):1173-83 PMID: 8636428
  5. Transforming growth factor beta 1 inhibits mitogen-activated protein kinase induced by basic fibroblast growth factor in smooth muscle cells.
    Biochem J. 1996 May 15;316 ( Pt 1):167-73 PMID: 8645201
  6. Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin.
    Am J Pathol. 1996 Jul;149(1):293-305 PMID: 8686754
  7. Control of adhesion-dependent cell survival by focal adhesion kinase.
    J Cell Biol. 1996 Aug;134(3):793-9 PMID: 8707856
  8. Suppression of p53 activity and p21WAF1/CIP1 expression by vascular cell integrin alphaVbeta3 during angiogenesis.
    J Clin Invest. 1996 Jul 15;98(2):426-33 PMID: 8755653
  9. The adaptor protein Shc couples a class of integrins to the control of cell cycle progression.
    Cell. 1996 Nov 15;87(4):733-43 PMID: 8929541
  10. Integrins can collaborate with growth factors for phosphorylation of receptor tyrosine kinases and MAP kinase activation: roles of integrin aggregation and occupancy of receptors.
    J Cell Biol. 1996 Dec;135(6 Pt 1):1633-42 PMID: 8978828
  11. Integrins and vascular extracellular matrix assembly.
    J Clin Invest. 1997 Mar 15;99(6):1149-52 PMID: 9077520
  12. Regulation of cell motility by mitogen-activated protein kinase.
    J Cell Biol. 1997 Apr 21;137(2):481-92 PMID: 9128257
  13. Induction of the angiogenic phenotype by Hox D3.
    J Cell Biol. 1997 Oct 6;139(1):257-64 PMID: 9314544
  14. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo.
    J Biol Chem. 1995 Nov 17;270(46):27489-94 PMID: 7499206
  15. Synthesis of antihemophilic factor antigen by cultured human endothelial cells.
    J Clin Invest. 1973 Nov;52(11):2757-64 PMID: 4583980
  16. Integrin (the CSAT antigen): functionality requires oligomeric integrity.
    J Cell Biol. 1986 Dec;103(6 Pt 1):2421-8 PMID: 3491082
  17. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor.
    J Biol Chem. 1987 Dec 25;262(36):17703-11 PMID: 2447074
  18. Human microvascular endothelial cells express integrin-related complexes that mediate adhesion to the extracellular matrix.
    J Cell Physiol. 1989 May;139(2):275-86 PMID: 2469686
  19. How does extracellular matrix control capillary morphogenesis?
    Cell. 1989 Sep 8;58(5):803-5 PMID: 2673531
  20. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF.
    Cell. 1991 May 17;65(4):663-75 PMID: 2032290
  21. Regulators of angiogenesis.
    Annu Rev Physiol. 1991;53:217-39 PMID: 1710435
  22. Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies.
    Cell Regul. 1991 May;2(5):357-71 PMID: 1654126
  23. Extracellular signal-regulated kinases: ERKs in progress.
    Cell Regul. 1991 Dec;2(12):965-78 PMID: 1801927
  24. Angiogenesis.
    J Biol Chem. 1992 Jun 5;267(16):10931-4 PMID: 1375931
  25. The beta-PDGF receptor induces neuronal differentiation of PC12 cells.
    Mol Biol Cell. 1992 May;3(5):545-53 PMID: 1319243
  26. Immunological characterization of avian MAP kinases: evidence for nuclear localization.
    Mol Biol Cell. 1992 Jul;3(7):775-87 PMID: 1325221
  27. Sustained activation of the mitogen-activated protein (MAP) kinase cascade may be required for differentiation of PC12 cells. Comparison of the effects of nerve growth factor and epidermal growth factor.
    Biochem J. 1992 Dec 1;288 ( Pt 2):351-5 PMID: 1334404
  28. Co-regulation of the mitogen-activated protein kinase, extracellular signal-regulated kinase 1, and the 90-kDa ribosomal S6 kinase in PC12 cells. Distinct effects of the neurotrophic factor, nerve growth factor, and the mitogenic factor, epidermal growth factor.
    J Biol Chem. 1993 May 5;268(13):9803-10 PMID: 8387505
  29. Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor.
    Cell. 1993 May 7;73(3):611-20 PMID: 8490966
  30. The extracellular matrix as a cell survival factor.
    Mol Biol Cell. 1993 Sep;4(9):953-61 PMID: 8257797
  31. Trk receptors use redundant signal transduction pathways involving SHC and PLC-gamma 1 to mediate NGF responses.
    Neuron. 1994 Mar;12(3):691-705 PMID: 8155326
  32. Neuronal differentiation signals are controlled by nerve growth factor receptor/Trk binding sites for SHC and PLC gamma.
    EMBO J. 1994 Apr 1;13(7):1585-90 PMID: 8156997
  33. Requirement of vascular integrin alpha v beta 3 for angiogenesis.
    Science. 1994 Apr 22;264(5158):569-71 PMID: 7512751
  34. Selective recognition of cyclic RGD peptides of NMR defined conformation by alpha IIb beta 3, alpha V beta 3, and alpha 5 beta 1 integrins.
    J Biol Chem. 1994 Aug 12;269(32):20233-8 PMID: 8051114
  35. Integrin alpha v beta 3 rescues melanoma cells from apoptosis in three-dimensional dermal collagen.
    Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8856-60 PMID: 7522323
  36. Integrin-mediated cell adhesion activates mitogen-activated protein kinases.
    J Biol Chem. 1994 Oct 28;269(43):26602-5 PMID: 7929388
  37. EGF triggers neuronal differentiation of PC12 cells that overexpress the EGF receptor.
    Curr Biol. 1994 Aug 1;4(8):694-701 PMID: 7953555
  38. Integrin-mediated signal transduction linked to Ras pathway by GRB2 binding to focal adhesion kinase.
    Nature. 1994 Dec 22-29;372(6508):786-91 PMID: 7997267
  39. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels.
    Cell. 1994 Dec 30;79(7):1157-64 PMID: 7528107
  40. Matrix/integrin interaction activates the mitogen-activated protein kinase, p44erk-1 and p42erk-2.
    J Biol Chem. 1995 Jan 6;270(1):269-73 PMID: 7814385
  41. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation.
    Cell. 1995 Jan 27;80(2):179-85 PMID: 7834738
  42. Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function.
    Science. 1995 Feb 10;267(5199):883-5 PMID: 7846531
  43. Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. Effect of actinomycin D and antisense oligonucleotides.
    J Biol Chem. 1995 Mar 31;270(13):7161-6 PMID: 7706254
  44. Integrin-dependent activation of MAP kinase: a link to shape-dependent cell proliferation.
    Mol Biol Cell. 1995 Mar;6(3):273-82 PMID: 7612963
  45. Definition of two angiogenic pathways by distinct alpha v integrins.
    Science. 1995 Dec 1;270(5241):1500-2 PMID: 7491498
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.140.5.1255
Published
1998-03-09
Pages
1255-63
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132684
Subset
IM
Grants
NHLBI NIH HHS · 1F32 HL09435 · United States
NCI NIH HHS · 1F32CA67442 · United States
NCI NIH HHS · CA50286 · United States
External Links
PubMed source DOI: 10.1083/jcb.140.5.1255 PMC Full Text View journal details
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