PathwayStep631 PathwayStep630 PathwayStep637 PathwayStep636 PathwayStep639 PathwayStep638 PathwayStep633 PathwayStep632 PathwayStep635 PathwayStep634 PathwayStep642 PathwayStep641 PathwayStep640 PathwayStep645 PathwayStep649 PathwayStep651 PathwayStep650 PathwayStep653 PathwayStep652 PathwayStep655 PathwayStep654 Release of CSK from SRC Clustering of Integrin alphaIIb beta3 complexes Interaction of integrin alphaIIb beta3 with Fibrinogen Integrin alphaIIb beta3 activation Activation of Talin Integrin alpha IIb beta3 T779 phosphorylation blocks SHC binding Phosphorylation of pFADK1 by SRC Dephosphorylation of inactive SRC by PTPB1 Autophosphorylation of SRC Translocation of FADK1 to Focal complexes Autophosphorylation of FADK1 at Y397 SYK activation by SRC SHC1 dissociates from integrin alphaIIb beta3 SYK binds to integrin alphaIIb beta3 Activated integrin alphaIIb beta3 binds SHC1 SHC1 bound to integrin alphaIIb beta3 is phosphorylated somehow Translocation of RIAM to plasma membrane Activation of Rap1 by membrane-associated GEFs Activation of Rap1 by cytosolic GEFs p130Cas linkage to MAPK signaling for integrins Integrin alphaIIb beta3 signaling At the sites of vascular injury bioactive molecules such as thrombin, ADP, collagen, fibrinogen and thrombospondin are generated, secreted or exposed. These stimuli activate platelets, converting the major platelet integrin alphaIIbbeta3 from a resting state to an active conformation, in a process termed integrin priming or ‘inside-out signalling’. Integrin activation refers to the change required to enhance ligand-binding activity. The activated alphaIIbbeta3 interacts with the fibrinogen and links platelets together in an aggregate to form a platelet plug. AlphaIIbbeta3 bound to fibrin generates more intracellular signals (outside-in signalling), causing further platelet activation and platelet-plug retraction. <br>In the resting state the alpha and beta tails are close together. This interaction keeps the membrane proximal regions in a bent conformation that maintains alphaIIbbeta3 in a low affinity state. <br>Integrin alphaIIbbeta3 is released from its inactive state by interaction with the protein talin. Talin interacts with the beta3 cytoplasmic domain and disrupts the salt bridge between the alpha and beta chains. This separation in the cytoplasmic regions triggers the conformational change in the extracellular domain that increases its affinity to fibrinogen. <br>Much of talin exists in an inactive cytosolic pool, and the Rap1 interacting adaptor molecule (RIAM) is implicated in talin activation and translocation to beta3 integrin cytoplasmic domain.<br> Authored: Garapati, P V, 2008-06-16 17:13:06 Edited: Garapati, P V, 2008-06-16 17:13:06 Pubmed10508650 Pubmed10605720 Pubmed14754902 Pubmed15205259 Pubmed16102042 Pubmed17624957 Reactome Database ID Release 43354192 Reactome, http://www.reactome.org ReactomeREACT_15523 Reviewed: Shattil, SJ, 2008-09-16 06:21:39 GRB2:SOS provides linkage to MAPK signaling for Intergrins