SHARPIN is an endogenous inhibitor of β1-integrin activation

摘要: Regulated activation of integrins is critical for cell adhesion, motility and tissue homeostasis. Talin kindlins activate β1-integrins, but the counteracting inhibiting mechanisms are poorly defined. We identified SHARPIN as an important inactivator β1-integrins in RNAi screen. inhibited β1-integrin functions human cancer cells primary leukocytes. Fibroblasts, leukocytes keratinocytes from SHARPIN-deficient mice exhibited increased activity, which was fully rescued by re-expression SHARPIN. found that directly binds to a conserved cytoplasmic region integrin α-subunits inhibits recruitment talin kindlin integrin. Therefore, switching inactive active conformations.