Figure 11.

Differentiation state-selective contributions of α2β1, α3β1, α5β1, and α6β4 integrins in the suppression of anoikis in human IECs. Schematic drawing of an undifferentiated IEC (A) and its differentiated counterpart (B), illustrating how α2β1, α3β1, α5β1, and α6β4 integrins contribute in the engagement of Fak/Src signaling for the suppression of anoikis. A. In undifferentiated IECs, α2β1 and α5β1 (but not α3β1) contribute in the engagement and activation of Fak (assessed by Y397 residue phosphorylation) via the classical requirement of both α and β subunits for integrin functionality and signalling. Fak then engages and activates Src (assessed by Y418 residue phosphorylation) which, in turn, enacts functional Fak-Src interactions (assessed by phosphorylation of Y576/577 residues of Fak). In parallel, α6β4ctd- engages and activates a distinct pool of Src that does not interact functionally with Fak. Furthermore, such Src engagement by α6β4ctd- is enacted in a primarily α6 subunit-dependent manner. B. In differentiated IECs, α3β1 (but not α2β1 or α5β1) engages and activates Fak, again via the classical requirement of both α and β subunits. Fak then engages and activates Src which, in turn, enacts functional Fak-Src interactions. However, in this context, Src contributes reciprocally to Fak activation. In parallel, α6β4 engages and activates a distinct pool of Src that does not interact functionally with Fak. Additionally, the engagement of Src by α6β4 is now enacted via the classical requirement of both α and β subunits. A-B. Such integrin subunit- and differentiation state-selective roles of α2β1, α3β1, α5β1, and α6β4 integrins, in the engagement of Fak and/or Src, are likely to contribute to the outcome of differentiated IECs being more sensitive to anoikis than their undifferentiated counterparts.

Beauséjour et al. BMC Cell Biology 2013 14:53   doi:10.1186/1471-2121-14-53
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