The Kindlin Family of Adapter Proteins

Abstract

A half century of research and more than 75,000 publications have cemented the foundational role of integrins as major conduits of communication between the extracellular environment and the interior of cells. By serving as cell-surface receptors for numerous extracellular ligands, integrin α and β heterodimers are integrally involved in the physiological and pathophysiological responses of virtually all cell types. Excessive or suppressed ligand binding to integrins are implicated in many diseases, including cancer, inflammation and cardiovascular diseases.

Keywords: amino acid sequence; endothelial cells; fibroblasts; integrins; leukocytes; platelets.

Figure.

Subdomain organization of Kindlin-2. (Top) Subdomains of Kindlin-2 and their corresponding sequence numbers. (Bottom) Crystal structure of Kindlin-2 (PDB code 5xpy) with subdomains highlighted. Note that F2-N is the N-terminal portion of F2 prior to PH domain since the structure lacks PH domain and C-terminal F2 part. Certain regions that are under investigation are highlighted by arrows including C-terminal helix that bridges F1 and F3; QW that interacts with integrin; and clathrin box that potentially binds to clathrin.