Identifiers
NAME:Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / ECM
References
PMID:10025398
Large latent complex binds to aVb6 via the RGD motif present in the LAP of TGFb, then
the b6 cytoplasmic domain binds to the actin cytoskeleton, then
Cytoskeleton-associated integrin induces release of mature TGFb from the large latent complex
PMID:21883891
This is one of the 2 mechanisms for activating TGFb via integrins.
In this model, there is no proteolysis of either the LAP or LTBP.
PMID:21900405
LAP contains an integrin-binding site called RBD
Several RBD-binding integrins are able to activate latent TGFB complex through binding this site.
PMID:21909923
The previously mentionned integrins are: a8b1, aVb1, aVb5, aVb6, aVb8.
In the complex Ingergin-large latent TGFB complex, I picked aVb6 as example. But a8b1, aVb1, aVb5, and aVb8 can active TGFB with the same mechanism.
em_emtc_emtc_re350( EMT Senescence ):
Several RBD-binding integrins are able to activate latnet TGFB complex through binding this site.
MMP13 activates TGFB by cleavage of LAP
Plasmin activates TGFB by cleavage of LAP
MMP9 activates TGFB by cleavage of LAP
Integrin aVb6 activates the ECM-bound latent TGFB1 and TGFB3 by traction, without participation of MMPs, so no hydrolyse or clevage
Integrin aVb8 and MMP14 (so-called MT1-MMP) cooperate to activate the ECM-bound latent TGFB1 and TGFB3:
-Integrin aVb8 binds LAP from the large latent complex
-MMP14 then is recruited to cleave LAP
→ Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*|hm2@Extracellular space + TGFB1|hm2|active@Extracellular space