Activated IRAK1/2, binds TRAF6, an E3 ubiquitin ligase, to the signalsome, and promotes the formation of an extended 2-D lattice formed by TRAF6-TRAF6 interactions.

TLS Online TPP Program

#Id: 9343

#XL - T Zoology

Prodomain forms disulfide linkages that localize the latent TGF-β to the surface of the secreting cell (GARP), to a nearby cell, or to the extracellular matrix (LTBP).

TLS Online TPP Program

#Id: 9345

#XL - T Zoology

TGF-β activation

By cytoskeletal force transmitted by integrins

TLS Online TPP Program

#Id: 9346

#XL - T Zoology

The prodomains of TGF-β1 and TGF-β3 contain a RGD motif, that allows them to bind to integrins.

TLS Online TPP Program

#Id: 9347

#XL - T Zoology

During cell migration, a tensile force is generated which physically distorts the prodomain and frees the active TGF-β dimer, initiating TGF-β signaling.

TLS Online TPP Program

#Id: 9348

#XL - T Zoology

3 separate TGF-β receptor proteins participate in binding TGF-β and activating signaling:

RI, RII, and RIII

TLS Online TPP Program

#Id: 9350

#XL - T Zoology

RI and RII receptors are homodimeric proteins with serine/threonine kinases in their cytosolic domains. 

(RI and RII sufficient to serve as a functional hetero-tetrameric TGF-β receptor)