Identifiers
NAME:LTBP1:Latency-associated protein*:TGFB1
Maps_Modules
HMC:ACTIVATING_INVASION_AND_METASTASIS
EMT Senescence / EMT_REGULATORS
EMT Senescence / ECM
References
PMID:15611103
PMID:21900405
TGFB is released from cells in a latent complex formed by 3 proteins:
(i) TGFB, (ii) the processed TGFB propeptide (LAP) and (iii) a member of the latent TGFB binding protein (LTBP) family
LTBPs are microfibril-associated proteins that tether latent TGFB to the ECM
em_emtc_emtc_re197( EMT Senescence ):
LAP contains an integrin-binding site called RBD
Several RBD-binding integrins are able to activate latnet 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.
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
em_emtc_emtc_re228( EMT Senescence ):
Integrin aVb6 activates the ECM-bound latent TGFB1 and TGFB3 by traction
+ LTBP1@Extracellular space → LTBP1:Latency-associated protein*|hm2:TGFB1|hm2@Extracellular space
+ LTBP1:Latency-associated protein*|hm2:TGFB1|hm2@Extracellular space → Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*|hm2:TGFB1|hm2@Extracellular space
→ TGFB1|hm2|active@Extracellular space + LTBP1:Latency-associated protein*|hm2@Extracellular space