PMID:18363565

Citation	Banno, A and Ginsberg, MH (2008) Integrin activation. Biochem. Soc. Trans. 36:229-34
Abstract	Agonist stimulation of integrin receptors, composed of transmembrane alpha and beta subunits, leads cells to regulate integrin affinity ('activation'), a process that controls cell adhesion and migration, and extracellular matrix assembly. A final step in integrin activation is the binding of talin to integrin beta cytoplasmic domains. We used forward, reverse and synthetic genetics to engineer and order integrin activation pathways of a prototypic integrin, platelet alphaIIbbeta3. PMA activated alphaIIbbeta3 only after expression of both PKCalpha (protein kinase Calpha) and talin at levels approximating those in platelets. Inhibition of Rap1 GTPase reduced alphaIIbbeta3 activation, whereas expression of constitutively active Rap1A(G12V) bypassed the requirement for PKCalpha. Overexpression of a Rap effector, RIAM (Rap1-GTP-interacting adaptor molecule), activated alphaIIbbeta3 and bypassed the requirement for PKCalpha and Rap1. In addition, shRNA (short hairpin RNA)-mediated knockdown of RIAM blocked talin interaction with and activation of integrin alphaIIbbeta3. Rap1 activation caused the formation of an 'activation complex' containing talin and RIAM that redistributed to the plasma membrane and activated alphaIIbbeta3. The central finding was that this Rap1-induced formation of an 'integrin activation complex' leads to the unmasking of the integrin-binding site on talin, resulting in integrin activation.
Links	PubMed PMC2588347 Online version:10.1042/BST0360229
Keywords	Adaptor Proteins, Signal Transducing/antagonists & inhibitors; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/metabolism; Humans; Membrane Proteins/antagonists & inhibitors; Membrane Proteins/genetics; Membrane Proteins/metabolism; Models, Biological; Platelet Glycoprotein GPIIb-IIIa Complex/agonists; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism; Protein Kinase C-alpha/metabolism; Signal Transduction/physiology; Talin/metabolism; rap1 GTP-Binding Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:AB1IP	Contributes to	GO:0033622: integrin activation	ECO:0000315:		P		Figure 2	complete CACAO 11267

References

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