Protein interactions with the cytoplasmic domains of αIIb or β3 regulate integrin signaling. Shown are some, but not all, of the proteins reported to associate with the αIIbβ3 cytoplasmic domains, many in a dynamic fashion. Some associate with αIIbβ3 in resting platelets, while others are recruited to, or dissociate from, the integrin during inside-out or outside-in signaling, leading to F-actin assembly. In addition, several proteins with enzymatic function become activated (asterisk) after fibrinogen binding to αIIbβ3. It is difficult to imagine that all of these proteins can interact with a single αIIbβ3 heterodimer in platelets; however, they might interact with and further regulate oligomers of αIIbβ3 that form in response to fibrinogen binding. Not shown are the many additional adapter molecules, enzymes and substrates that may become recruited through more indirect interactions during the various phases of integrin signaling. Abbreviations: PP1c, protein phosphatase 1c; RACK1, receptor for activated C kinase 1; Csk, c-Src tyrosine kinase; PKCβ, protein kinase Cβ; ILK, integrin-linked kinase; ITAM, a yet-to-be-identified protein with one or more immunoreceptor tyrosine activation motifs; CIB, calcium and integrin-binding 1; Syk, spleen tyrosine kinase.