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Integrin signaling

Summary

Organism

Homo sapiens (human)

Reactome

R-HSA-354192

PubChem

R-HSA-354192

Description

Integrins are a major family of cell surface receptors that modulate cell adhesion, migration, proliferation and survival through interaction with the extracellular matrix (ECM) and the actin cytoskeleton. Integrins are type 1 transmembrane proteins that exist at the cell surface as heterodimers of alpha and beta subunits, of which there are 18 and 8 different isoforms, respectively, in human cells. In addition to their mechanical role in mediating contact between the ECM and the cytoskeleton, integrins also modulate intracellular signaling pathways governing cytoskeletal rearrangements and pro-survival and mitogenic signaling (reviewed in Hehlgans et al, 2007; Harburger and Calderwood, 2009; Ata and Antonescu, 2017).
In this pathway, we describe signaling through integrin alphaIIb beta3 as a representative example.
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.
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.
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.
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.

Click on a node on the pathway to see its details. Glycoproteins are marked with a glycoprotein icon in their name.

SPV: a JavaScript Signaling Pathway Visualizer, Bioinformatics, 2018

Displaying entries **1 - 10** of 17 in total

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UniProt ID	Protein Name	Gene Symbol	Pathway Viewer
O15530	3-phosphoinositide-dependent protein kinase 1	PDK1 PDPK1	view
O95398	Rap guanine nucleotide exchange factor 3	CGEF1 EPAC EPAC1 RAPGEF3	view
P02671	Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain]	FGA	view
P02675	Fibrinogen beta chain [Cleaved into: Fibrinopeptide B; Fibrinogen beta chain]	FGB HEL-S-78p	view
P02679	Fibrinogen gamma chain	FGG PRO2061	view
P02751	Fibronectin	FN FN1	view
P04275	von Willebrand factor	F8VWF VWF	view
P05106	Integrin beta-3	GP3A ITGB3	view
P08514	Integrin alpha-IIb	GP2B ITGA2B ITGAB	view
P12931	Proto-oncogene tyrosine-protein kinase Src	SRC SRC1	view

Displaying **all 3** entries
GlyCosmos Lectin	UniProt ID	Lectin Name	Pathway Viewer
GL_005388	P02671	Fibrinogen alpha chain [Cleaved into: Fibrinopeptide A; Fibrinogen alpha chain]	view
GL_005389	P02675	Fibrinogen beta chain [Cleaved into: Fibrinopeptide B; Fibrinogen beta chain]	view
GL_005390	P02679	Fibrinogen gamma chain	view

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