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Related Experiment Videos

A regulated interaction between alpha5beta1 integrin and osteopontin.

S T Barry1, S B Ludbrook, E Murrison

  • 1Molecular Pharmacology, Glaxo Wellcome Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, United Kingdom. stb38557@glaxowellcome.co.uk

Biochemical and Biophysical Research Communications
|February 16, 2000
PubMed
Summary
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Osteopontin (OPN) cleavage by thrombin enhances its interaction with alpha5beta1 integrins. This binding is dependent on the RGD motif and can be activated by TPA or alpha4beta1 integrin expression.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Integrin Signaling

Background:

  • Osteopontin (OPN) is an extracellular matrix protein known to interact with various integrins.
  • The interaction of OPN with specific integrins is crucial for cellular processes like adhesion and migration.
  • The activation state of integrins significantly influences their binding affinity to ligands.

Purpose of the Study:

  • To investigate the interaction between alpha5beta1 integrin and osteopontin (OPN).
  • To determine the role of OPN cleavage and integrin activation in this interaction.
  • To elucidate the mechanism by which alpha4beta1 integrin influences alpha5beta1 binding to OPN.

Main Methods:

  • Utilized K562 cells, which naturally express alpha5beta1 integrin.

Related Experiment Videos

  • Stimulated alpha5beta1 integrin activation using the phorbol ester TPA.
  • Employed a GST fusion protein of the N-terminal OPN fragment (aa17-168) generated by thrombin cleavage.
  • Investigated the effect of expressing alpha4beta1 integrin in K562 cells.
  • Assessed the role of the Arg-Gly-Asp (RGD) motif in OPN binding through mutagenesis (RAD).

    • Main Results:

    • Alpha5beta1 integrin interaction with OPN was observed in K562 cells only upon TPA-induced high activation state.
    • Alpha5beta1 integrin selectively bound to the thrombin-cleaved N-terminal fragment of OPN (aa17-168).
    • Expression of alpha4beta1 integrin in K562 cells promoted alpha5beta1-dependent binding to OPN fragment aa17-168 without TPA.
    • The Arg-Gly-Asp (RGD) motif within OPN was essential for alpha5beta1-mediated adhesion, as its mutation to RAD abolished binding.

    Conclusions:

    • Thrombin cleavage of OPN regulates its adhesive properties.
    • Alpha5beta1 integrin can bind to thrombin-cleaved OPN when in a high activation state.
    • Alpha4beta1 integrin can act as an activating receptor for alpha5beta1 in the context of OPN binding.