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Table 1.

Kindlin regulation mechanisms

Domains/sites Regulation mechanism Functional outcomes
F0 Binds to negatively charged PIP2, paxillin, and leupaxin Integrin activation
Binds to Asp709 in β2 and unclasps salt bridge in IMC H+
F1 Binds Arp2/3 (kindlin-2) FA targeting and integrin activation
F1 loop Binds membrane lipids FA targeting of kindlins; not known for kindlin-3
F2 Binds to ILK Recruitment to the plasma membrane.
Outside-in signaling via ILK-Pinch-Parvin complex
Dimerization through F2-F2 interaction Integrin clustering and avidity regulation
PH domain Binds PIP2 and PIP3 Facilitates kindlin-3 recruitment to plasma membrane
In homotrimer, binds F3 Masks the integrin binding sites, resulting in autoinhibition
Oligomerization via PH domain Negatively regulates integrin binding
F3 Binds integrin tail Activates integrins
Phosphorylation sites Phosphorylation site S485 Facilitates kindlin recruitment and integrin activation

FA, focal adhesion.