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Figure 1

Mechanisms proposed for growth factor signalling regulation by integrins. (A) The repertoire of integrins expressed on a particular cell can specify the signal pathway due to the differential binding affinity of ECM ligands for the integrins. The tissue stiffness and matrix composition can initiate specific signalling pathways regulating cell behaviour. Clustering and activation of the integrins/actin complexes strengthen the focal adhesion interaction and initiate the framework for cell signalling through assembly of adhesomes. (B) Integrins, via their cytoplasmic domain, recruit specific adaptors to the plasma membrane, which regulate the growth factor receptor signalling. For example, β1c integrin recruits Gab1/Shp2 and presents Shp2 to IGF1R, resulting in dephosphorylation of the receptor (Goel et al. 2005). (C) In response to growth factor stimulation, integrins co-localise at focal adhesion with the growth factor receptors and their associated signalling molecules, such as Src and FAK, as well as with cytoskeletal molecules such as paxillin, talin, and vinculin. For example, the α2β1 integrin co-localises with EGFR (Yu et al. 2000), which eventually regulate the activity of the downstream effectors such as ERK, AKT, JNK, and the Rho GTPases. The details of these downstream pathways can be found in other recent reviews (Legate et al. 2009). (D) Integrins can change the rate of growth factor receptor internalisation and degradation. One such example is the interaction of EGFR1 and α5β1 integrin, which is co-ordinately recycled to the plasma membrane, regulating the protein kinase B (PKB) signalling (Caswell et al. 2009). Integrin-mediated cell adhesion can also alter PDGFR rate of degradation via ubiquitination (Baron & Schwartz 2000).

This Article

  1. Published online before print February 9, 2011, doi: 10.1530/JOE-10-0377 J Endocrinol vol. 209 no. 2 139-151
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