Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*:TGFB1

Complex Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*:TGFB1 map


Complex composition:

  1. Latency-associated protein* map
  2. TGFB1 map
  3. LTBP1 map
  4. Integrin A8B1_AVB1_AVB5_AVB6_AVB8* map




Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space

Identifiers
NAME:Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:LTBP1:Latency-associated protein*:TGFB1

Maps_Modules
 EMT  map  / ECM  map

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.
e_re197( EMT  map ):
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
e_re198( EMT  map ):
PMID:18342983
Two main models are proposed how integrins contribute to latent TGFB1 activation:
(1) In a protease-dependent mechanism, integrins avb8and avb3 are suggested to simultaneously bind the latent TGFB1 complex and proteinases.
This close vicinity at the cell surface improves enzymatic cleavage of the latent complex to release active TGFB1.
(2) Integrins avb3, avb5, avb6, and avb8 appear to change the conformation of the latent TGFB1 complex by transmitting cell traction forces.
PMID:19854168
Integrins are linked intracellularly to cytoskleletal elements and associated contractile machinery, and extracellularly to ECM.
Thus contractility of a cell bound to a rigid ECM generates force between a matrix molecule and its receptor. Such forces may uncouple LLCs so as to free TGFb.
PMID:16710477
The small GTPase RhoA has well established roles in contractility and has been shown to promote TGFb activation from LLCs.

Confidence
REF=2 FUNC=4


Modifications:
Participates in complexes:
In compartment: Extracellular space
  1. Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map

Participates in reactions:
As Reactant or Product:

  1. Integrin A8B1_AVB1_AVB5_AVB6_AVB8*@Extracellular space map + LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map

  2. Actin cytoskeletal*@Cytoplasm map + Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map map Actin cytoskeletal*:​Integrin A8B1_AVB1_AVB5_AVB6_AVB8*:​LTBP1:​Latency-associated protein*|​hm2:​TGFB1|​hm2@Extracellular space map

As Catalyser:

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