Suppression of integrin function. (A) Cytoplasmic proteins can negatively regulate integrin function through stabilization of the bent integrin conformation, sequestration, or inactivation of integrin activators, such as Rap1, or direct binding to integrin cytoplasmic tails, which may hinder the binding of integrin activators, such as talin and kindlin. (B) Extracellular and cell surface proteins can negatively affect integrin function by preventing inside-out or outside-in signaling. CSK, C-terminal Src kinase; GDF, growth/differentiation factor; ITIM, immunoreceptor tyrosine-based inhibitory motif; JAM-A, junctional adhesion molecule-A; NE, norepinephrine; PG, prostaglandin; SHIP, SH2 domain-containing inositol 5-phosphatase; SIRPα, signal regulatory protein α; TGF-βR, TGF-β receptor.