Negative regulators of integrin activity

Jeroen Pouwels, Jonna Nevo, Teijo Pellinen, Jari Ylänne, Johanna Ivaska

Research output: Contribution to journalArticleScientificpeer-review

25 Citations (Scopus)

Abstract

Integrins are heterodimeric transmembrane adhesion receptors composed of α- and β-subunits. They are ubiquitously expressed and have key roles in a number of important biological processes, such as development, maintenance of tissue homeostasis and immunological responses. The activity of integrins, which indicates their affinity towards their ligands, is tightly regulated such that signals inside the cell cruicially regulate the switching between active and inactive states. An impaired ability to activate integrins is associated with many human diseases, including bleeding disorders and immune deficiencies, whereas inappropriate integrin activation has been linked to inflammatory disorders and cancer. In recent years, the molecular details of integrin ‘inside-out’ activation have been actively investigated. Binding of cytoplasmic proteins, such as talins and kindlins, to the cytoplasmic tail of β-integrins is widely accepted as being the crucial step in integrin activation. By contrast, much less is known with regard to the counteracting mechanism involved in switching integrins into an inactive conformation. In this Commentary, we aim to discuss the known mechanisms of integrin inactivation and the molecules involved.
Original languageEnglish
Pages (from-to)3271-3280
JournalJournal of Cell Science
Volume125
Issue number14
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Integrins
Talin
Biological Phenomena
Immune System Diseases
Tail
Carrier Proteins
Homeostasis
Maintenance
Hemorrhage
Ligands

Keywords

  • Activation
  • adhesion
  • endocytosis
  • integrin
  • SHARPIN
  • talin

Cite this

Pouwels, J., Nevo, J., Pellinen, T., Ylänne, J., & Ivaska, J. (2012). Negative regulators of integrin activity. Journal of Cell Science, 125(14), 3271-3280. https://doi.org/10.1242/jcs.093641
Pouwels, Jeroen ; Nevo, Jonna ; Pellinen, Teijo ; Ylänne, Jari ; Ivaska, Johanna. / Negative regulators of integrin activity. In: Journal of Cell Science. 2012 ; Vol. 125, No. 14. pp. 3271-3280.
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Pouwels, J, Nevo, J, Pellinen, T, Ylänne, J & Ivaska, J 2012, 'Negative regulators of integrin activity', Journal of Cell Science, vol. 125, no. 14, pp. 3271-3280. https://doi.org/10.1242/jcs.093641

Negative regulators of integrin activity. / Pouwels, Jeroen; Nevo, Jonna; Pellinen, Teijo; Ylänne, Jari; Ivaska, Johanna.

In: Journal of Cell Science, Vol. 125, No. 14, 2012, p. 3271-3280.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Negative regulators of integrin activity

AU - Pouwels, Jeroen

AU - Nevo, Jonna

AU - Pellinen, Teijo

AU - Ylänne, Jari

AU - Ivaska, Johanna

PY - 2012

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AB - Integrins are heterodimeric transmembrane adhesion receptors composed of α- and β-subunits. They are ubiquitously expressed and have key roles in a number of important biological processes, such as development, maintenance of tissue homeostasis and immunological responses. The activity of integrins, which indicates their affinity towards their ligands, is tightly regulated such that signals inside the cell cruicially regulate the switching between active and inactive states. An impaired ability to activate integrins is associated with many human diseases, including bleeding disorders and immune deficiencies, whereas inappropriate integrin activation has been linked to inflammatory disorders and cancer. In recent years, the molecular details of integrin ‘inside-out’ activation have been actively investigated. Binding of cytoplasmic proteins, such as talins and kindlins, to the cytoplasmic tail of β-integrins is widely accepted as being the crucial step in integrin activation. By contrast, much less is known with regard to the counteracting mechanism involved in switching integrins into an inactive conformation. In this Commentary, we aim to discuss the known mechanisms of integrin inactivation and the molecules involved.

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KW - endocytosis

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Pouwels J, Nevo J, Pellinen T, Ylänne J, Ivaska J. Negative regulators of integrin activity. Journal of Cell Science. 2012;125(14):3271-3280. https://doi.org/10.1242/jcs.093641