Table 1. Kindlin regulation mechanisms... | American Society of Hematology

Table 1.

Kindlin regulation mechanisms

Domains/sites	Regulation mechanism	Functional outcomes
F0	Binds to negatively charged PIP2, paxillin, and leupaxin	Integrin activation
F0	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
F2	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

Domains/sites	Regulation mechanism	Functional outcomes
F0	Binds to negatively charged PIP2, paxillin, and leupaxin	Integrin activation
F0	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
F2	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.