Differences in α-β transmembrane domain interactions among integrins enable diverging integrin signaling

Chungho Kim, Min Cheol Kim

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Integrins are transmembrane adhesion molecules composed of α and β subunits. In humans, 24 integrins are expressed in a tissue-specific manner. Each integrin plays a specific role within a tissue type to control cell adhesion. We previously found that the degree of transmembrane domain (TMD) interaction between the integrin αIIb and β3 subunits is reversely correlated with the affinity of integrin αIIbβ3 to its ligand. Here, we examined the TMD interactions of various integrins, including α4β1, αLβ2, α5β1, αVβ1, αIIbβ3, and αVβ3. Our findings revealed that the degree of the TMD interactions in integrins α4β1 and αLβ2 expressed in immune cells was low and in integrins αIIbβ3 and αVβ3 expressed in platelets was high, while integrins α5β1 and αVβ1 that are expressed in most adherent cells displayed intermediate TMD interactions. We identified sequence variation within the N-terminal TMD region as a factor responsible for the observed differential degree of TMD interaction among integrins. When the N-terminal interaction that was missing in integrin α5β1 was restored with mutagenesis, the increase in TMD interaction inhibited the outside-in but not inside-out signaling of integrin α5β1 and also accelerated the speed of cell migration. We suggest, therefore, that the degree of TMD interaction is designed to accommodate the specific, desired function of each integrin.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalBiochemical and biophysical research communications
Issue number3
Publication statusPublished - 2013 Jul 5

Bibliographical note

Funding Information:
We thank Dr. Eun-Gyung Cho for her critical review of our manuscript. This work was supported in part by a Korea University Grant.


  • Integrin
  • Integrin activation
  • Migration
  • Outside-in signaling
  • Transmembrane domain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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