Integrin cytoplasmic domains may interact directly with serveral different cytoskeletal proteins and intracellular signaling molecules. Also, integrins interact directly with other transmembrane structures, including transmembrane-4 superfamily (TM4SF) proteins. New evidence suggests that TM4SF proteins may act as linkers between extracellular integrin alpha chain domains and intracellular signaling molecules, such as phosphatidylinositol 4-kinase and protein kinase C.