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Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies
13:52

Efficient Production and Purification of Recombinant Murine Kindlin-3 from Insect Cells for Biophysical Studies

Published on: March 19, 2014

Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1

Zheng-Kai Teng1, Neeru Arya1, Yinghui Li2

  • 1School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.

The Journal of Biological Chemistry
|May 15, 2026
PubMed

Kindlins are adaptor proteins that function synergistically with talin to activate integrins, facilitating cell adhesion and migration. In addition to this role, kindlins have other functions. In immune cells, kindlin-3 is the predominant kindlin paralog. Loss of kindlin-3 due to gene mutations leads to a bleeding disorder and impaired immune function, as observed in patients with leukocyte adhesion deficiency type III (LAD-III). In this study, we demonstrate that kindlin-3 maintains IL-2Rβ at the plasma membrane, a process that relies on the integrin LFA-1. This retention supports IL-2 signaling and helps protect natural killer (NK) cells from apoptosis when IL-2 levels are low. Kindlin-3 also promotes the colocalization of integrin LFA-1 and IL-2Rβ at sites where LFA-1 engages its ligand. Mechanistically, kindlin-3 directly binds the cytoplasmic domain of the interleukin-2 receptor β chain (IL-2Rβ) via its F0 subdomain. This interaction specifically targets a membrane-distal region of IL-2Rβ (residues 530-551) with micromolar affinity. Therefore, kindlin-3 acts as a bridging molecule that connects IL-2Rβ to the integrin LFA-1, thereby potentially coordinating cell adhesion with cytokine signaling.

Keywords:
cell adhesionintegrinsinterleukin 2 receptorinterleukin 2 signalingkindlins

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