Home LiteratureArticle Details
PMID: 11598197 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Cross talk between beta(1) and alpha(V) integrins: beta(1) affects beta(3) mRNA stability.

Molecular biology of the cell ·Vol. 12 ·No. 10 ·2001-10-00 ·Pages 3126-38

Retta SF, Cassarà G, D'Amato M, Alessandro R, Pellegrino M, Degani S, De Leo G, Silengo L, Tarone G

Abstract

There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of beta(1)-null GD25 cells ectopically expressing the beta(1)A integrin subunit, we provide evidence for the existence of a cross talk between beta(1) and alpha(V) integrins that affects the ratio of alpha(V)beta(3) and alpha(V)beta(5) integrin cell surface levels. In particular, we demonstrate that a down-regulation of alpha(V)beta(3) and an up-regulation of alpha(V)beta(5) occur as a consequence of beta(1)A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms beta(1)B and beta(1)D, as well as two beta(1) cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (beta(1)TR) or only its "variable" region (beta(1)COM), we show that the effects of beta(1) over alpha(V) integrins take place irrespective of the type of beta(1) isoform, but require the presence of the "common" region of the beta(1) cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby beta(1) integrins exert their trans-acting functions, we have found that the down-regulation of alpha(V)beta(3) is due to a decreased beta(3) subunit mRNA stability, whereas the up-regulation of alpha(V)beta(5) is mainly due to translational or posttranslational events. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.

MeSH Terms
Animals Antigens, CD/metabolism Antigens, Surface/metabolism Cell Adhesion/physiology Cells, Cultured/cytology,metabolism Cytoplasm/metabolism Fibroblasts/cytology,metabolism Integrin alphaV Integrin beta Chains Integrin beta1/metabolism Integrin beta3 Integrins/agonists,drug effects,metabolism Mice Platelet Membrane Glycoproteins/metabolism Protein Structure, Tertiary/physiology RNA Stability/physiology RNA, Messenger/metabolism Receptors, Vitronectin/antagonists & inhibitors,metabolism Subcellular Fractions/metabolism Up-Regulation/drug effects
Chemicals
Antigens, CD Antigens, Surface Integrin alphaV Integrin beta Chains Integrin beta1 Integrin beta3 Integrins Platelet Membrane Glycoproteins RNA, Messenger Receptors, Vitronectin integrin alphaVbeta5 integrin beta5
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Retta S F
Department of Genetics, Biology, and Biochemistry, University of Torino, 10126 Torino, Italy. francesco.ritto@unito.it
Cassarà G
D'Amato M
Alessandro R
Pellegrino M
Degani S
De Leo G
Silengo L
Tarone G
References (69)
69 references, click to expand
  1. Requirement of vascular integrin alpha v beta 3 for angiogenesis.
    Science. 1994 Apr 22;264(5158):569-71 PMID: 7512751
  2. Beta1B integrin interferes with matrix assembly but not with confluent monolayer polarity, and alters some morphogenetic properties of FRT epithelial cells.
    Eur J Cell Biol. 1998 Feb;75(2):107-17 PMID: 9548368
  3. Differential mRNA regulation of integrin subunits alpha V, beta 1, beta 3, and beta 5 during mouse embryonic organogenesis.
    Cell Adhes Commun. 1995 Nov;3(4):311-25 PMID: 8821033
  4. Integrins: regulators of embryogenesis.
    Biol Cell. 2000 Jan;92(1):5-25 PMID: 10761694
  5. The inhibition of vascular smooth muscle cell migration by peptide and antibody antagonists of the alphavbeta3 integrin complex is reversed by activated calcium/calmodulin- dependent protein kinase II.
    J Clin Invest. 1997 Aug 1;100(3):693-704 PMID: 9239418
  6. Transient functional expression of alphaVbeta 3 on vascular cells during wound repair.
    Am J Pathol. 1996 May;148(5):1407-21 PMID: 8623913
  7. Involvement of integrin alphavbeta3 in cell adhesion, motility, and liver metastasis of murine RAW117 large cell lymphoma.
    Cancer Res. 1996 Jul 1;56(13):3103-11 PMID: 8674068
  8. Muscle beta1D integrin reinforces the cytoskeleton-matrix link: modulation of integrin adhesive function by alternative splicing.
    J Cell Biol. 1997 Dec 15;139(6):1583-95 PMID: 9396762
  9. Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed cell motility but not adhesion on vitronectin.
    J Cell Biol. 1994 Nov;127(3):859-66 PMID: 7525598
  10. beta1-integrin cytoplasmic subdomains involved in dominant negative function.
    Mol Biol Cell. 1998 Apr;9(4):715-31 PMID: 9529373
  11. Re-epithelialization of normal human excisional wounds is associated with a switch from alpha v beta 5 to alpha v beta 6 integrins.
    Br J Dermatol. 1996 Jul;135(1):46-51 PMID: 8776358
  12. Integrin cytoplasmic domain-binding proteins.
    J Cell Sci. 2000 Oct;113 ( Pt 20):3563-71 PMID: 11017872
  13. Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells.
    J Invest Dermatol. 1992 Dec;99(6):715-22 PMID: 1281860
  14. Integrin alpha v beta 3 differentially regulates adhesive and phagocytic functions of the fibronectin receptor alpha 5 beta 1.
    J Cell Biol. 1994 Nov;127(4):1129-37 PMID: 7525603
  15. Requirement of the integrin beta 3 subunit for carcinoma cell spreading or migration on vitronectin and fibrinogen.
    J Cell Biol. 1992 Jun;117(5):1101-7 PMID: 1374415
  16. 1 alpha,25-dihydroxyvitamin D3 up-regulates expression of the osteoclast integrin alpha v beta 3.
    J Biol Chem. 1993 Jan 15;268(2):1456-61 PMID: 7678259
  17. Focal adhesion and stress fiber formation is regulated by tyrosine phosphatase activity.
    Exp Cell Res. 1996 Dec 15;229(2):307-17 PMID: 8986614
  18. Focal adhesions - the cytoskeletal connection.
    Curr Opin Cell Biol. 2000 Feb;12(1):133-9 PMID: 10679361
  19. Extracellular matrix alters PDGF regulation of fibroblast integrins.
    J Cell Biol. 1996 Jan;132(1-2):239-49 PMID: 8567727
  20. beta1D integrin inhibits cell cycle progression in normal myoblasts and fibroblasts.
    J Biol Chem. 1998 Jun 12;273(24):15234-40 PMID: 9614138
  21. Integrins and cancer.
    Curr Opin Cell Biol. 1996 Oct;8(5):724-30 PMID: 8939661
  22. Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins.
    Cell. 1998 Nov 13;95(4):507-19 PMID: 9827803
  23. Integrin cross talk: activation of lymphocyte function-associated antigen-1 on human T cells alters alpha4beta1- and alpha5beta1-mediated function.
    J Cell Biol. 1997 Sep 22;138(6):1437-47 PMID: 9298996
  24. Control of integrin expression by extracellular matrix.
    J Biol Chem. 1995 Nov 10;270(45):26794-801 PMID: 7592919
  25. Bidirectional signaling between the cytoskeleton and integrins.
    Curr Opin Cell Biol. 1999 Apr;11(2):274-86 PMID: 10209151
  26. p125FAK tyrosine phosphorylation and focal adhesion assembly: studies with phosphotyrosine phosphatase inhibitors.
    Exp Cell Res. 1995 Nov;221(1):141-52 PMID: 7589239
  27. Overlapping and independent functions of fibronectin receptor integrins in early mesodermal development.
    Dev Biol. 1999 Nov 15;215(2):264-77 PMID: 10545236
  28. Tumor necrosis factor alpha and interferon gamma modulate the expression of the vitronectin receptor (integrin beta 3) in human endothelial cells.
    J Biol Chem. 1991 Apr 25;266(12):7638-45 PMID: 1708389
  29. Protein kinase C regulates alpha v beta 5-dependent cytoskeletal associations and focal adhesion kinase phosphorylation.
    J Cell Biol. 1996 Sep;134(5):1323-32 PMID: 8794871
  30. Integrin expression in human melanoma cell lines: heterogeneity of vitronectin receptor composition and function.
    Int J Cancer. 1991 Dec 2;49(6):924-31 PMID: 1720426
  31. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression.
    Cancer Res. 1990 Oct 15;50(20):6757-64 PMID: 2208139
  32. Beta 1 integrin-dependent and -independent polymerization of fibronectin.
    J Cell Biol. 1996 Jan;132(1-2):227-38 PMID: 8567726
  33. Expression and cellular distribution of alpha(v)integrins in beta(1)integrin-deficient embryonic stem cell-derived cardiac cells.
    J Mol Cell Cardiol. 2001 Mar;33(3):521-32 PMID: 11181020
  34. The muscle-specific laminin receptor alpha7 beta1 integrin negatively regulates alpha5 beta1 fibronectin receptor function.
    Exp Cell Res. 1999 Feb 1;246(2):421-32 PMID: 9925758
  35. The structural bases of integrin-ligand interactions.
    Trends Cell Biol. 1994 Jul;4(7):256-61 PMID: 14731666
  36. Purification of fibronectin from human plasma.
    Methods Mol Biol. 1999;96:119-24 PMID: 10098128
  37. Genetic analysis of beta1 integrin function: confirmed, new and revised roles for a crucial family of cell adhesion molecules.
    J Cell Sci. 1997 Dec;110 ( Pt 23):2895-904 PMID: 9359872
  38. Complexity and specificity of integrin signalling.
    Nat Cell Biol. 2000 Jan;2(1):E13-4 PMID: 10620816
  39. Integrin signaling.
    Science. 1999 Aug 13;285(5430):1028-32 PMID: 10446041
  40. Alternatively spliced variants: a new view of the integrin cytoplasmic domain.
    Matrix Biol. 1997 Oct;16(4):185-93 PMID: 9402008
  41. Integrin alpha subunit ratios, cytoplasmic domains, and growth factor synergy regulate muscle proliferation and differentiation.
    J Cell Biol. 1996 Apr;133(1):169-84 PMID: 8601606
  42. Integrins alpha v beta 3 and alpha v beta 5 contribute to cell attachment to vitronectin but differentially distribute on the cell surface.
    J Cell Biol. 1991 May;113(4):919-29 PMID: 1709170
  43. Suprabasal integrin expression in the epidermis of transgenic mice results in developmental defects and a phenotype resembling psoriasis.
    Cell. 1995 Dec 15;83(6):957-68 PMID: 8521519
  44. Differential expression of alphav integrins in K1735 melanoma cells.
    Invasion Metastasis. 1998;18(1):1-14 PMID: 10207246
  45. Cell adhesion: old and new questions.
    Trends Cell Biol. 1999 Dec;9(12):M33-7 PMID: 10611678
  46. Integrin beta cytoplasmic domains differentially bind to cytoskeletal proteins.
    J Biol Chem. 1998 Mar 13;273(11):6104-9 PMID: 9497328
  47. Mouse myoblasts can fuse and form a normal sarcomere in the absence of beta1 integrin expression.
    J Cell Sci. 1998 Aug;111 ( Pt 16):2397-409 PMID: 9683634
  48. Targeted mutations in cell adhesion genes: what have we learned from them?
    Dev Biol. 1996 Dec 15;180(2):402-12 PMID: 8954713
  49. Integrin function and regulation in development.
    Int J Dev Biol. 2000;44(6):725-31 PMID: 11061437
  50. Integrins: versatility, modulation, and signaling in cell adhesion.
    Cell. 1992 Apr 3;69(1):11-25 PMID: 1555235
  51. The distribution of distinct integrins in focal contacts is determined by the substratum composition.
    J Cell Sci. 1989 Jan;92 ( Pt 1):67-75 PMID: 2476453
  52. Expression of beta 1B integrin isoform in CHO cells results in a dominant negative effect on cell adhesion and motility.
    J Cell Biol. 1994 Oct;127(2):557-65 PMID: 7523423
  53. Messenger RNA degradation in eukaryotes.
    Cell. 1993 Aug 13;74(3):413-21 PMID: 7688664
  54. Fibronectin receptor functions in embryonic cells deficient in alpha 5 beta 1 integrin can be replaced by alpha V integrins.
    Mol Biol Cell. 1996 Nov;7(11):1737-48 PMID: 8930896
  55. The alphavbeta3 integrin regulates alpha5beta1-mediated cell migration toward fibronectin.
    J Biol Chem. 1997 Nov 14;272(46):29380-9 PMID: 9361020
  56. Beta3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival.
    J Clin Invest. 1999 Jan;103(2):229-38 PMID: 9916135
  57. Integrin signaling: specificity and control of cell survival and cell cycle progression.
    Curr Opin Cell Biol. 1997 Oct;9(5):691-700 PMID: 9330873
  58. Basic fibroblast growth factor increases expression of the alpha v beta 3 integrin complex on human microvascular endothelial cells.
    J Invest Dermatol. 1994 Sep;103(3):295-9 PMID: 8077694
  59. Beta3 integrin activation improves alphavbeta3-mediated retraction of fibrin matrices.
    J Surg Res. 1999 May 1;83(1):27-31 PMID: 10210638
  60. Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
    J Clin Invest. 2000 Feb;105(4):433-40 PMID: 10683372
  61. 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
  62. A molecular mechanism of integrin crosstalk: alphavbeta3 suppression of calcium/calmodulin-dependent protein kinase II regulates alpha5beta1 function.
    J Cell Biol. 1999 May 17;145(4):889-97 PMID: 10330414
  63. Knockout and knockin of the beta1 exon D define distinct roles for integrin splice variants in heart function and embryonic development.
    Genes Dev. 1998 Apr 15;12(8):1202-16 PMID: 9553049
  64. The regulation of expression of integrin receptors.
    Proc Soc Exp Biol Med. 1997 Feb;214(2):123-31 PMID: 9034129
  65. Fibrin and collagen differentially regulate human dermal microvascular endothelial cell integrins: stabilization of alphav/beta3 mRNA by fibrin1.
    J Invest Dermatol. 1999 Dec;113(6):913-9 PMID: 10594730
  66. Definition of two angiogenic pathways by distinct alpha v integrins.
    Science. 1995 Dec 1;270(5241):1500-2 PMID: 7491498
  67. Genetic analyses of integrin function in mice.
    Curr Opin Cell Biol. 1996 Oct;8(5):641-6 PMID: 8939651
  68. Regulation of vascular smooth muscle cell integrin expression by transforming growth factor beta1 and by platelet-derived growth factor-BB.
    J Cell Physiol. 1992 Jun;151(3):588-95 PMID: 1295906
  69. Identification of a new biological function for the integrin alpha v beta 3: initiation of fibronectin matrix assembly.
    Cell Adhes Commun. 1996 Sep;4(3):149-58 PMID: 8969861
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.12.10.3126
Email
francesco.ritto@unito.it
Published
2001-10-00
Pages
3126-38
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC60161
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.12.10.3126 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2