Latent transforming growth factor beta complex (Latent TGF-beta complex)

The Latent transforming growth factor beta (TGF-beta) complex is the inactive precursor form of the TGF-beta cytokine, essential for controlling the bioavailability of this potent signaling molecule. It consists of a mature TGF-beta homodimer non-covalently bound to the Latency Associated Peptide (LAP), forming the Small Latent Complex (SLC). In many tissues, the SLC is further linked to Latent TGF-beta Binding Proteins (LTBPs) or the cell-surface protein GARP, creating the Large Latent Complex (LLC) that anchors the cytokine to the extracellular matrix or immune cell surfaces (Robertson & Rifkin, 2016). Activation of the complex is a tightly regulated process often mediated by integrins (such as alpha-v-beta-6 and alpha-v-beta-8) or proteases, which release the active TGF-beta to initiate downstream signaling via SMAD proteins (UniProt Consortium, 2024). Pathological over-activation of the latent complex is a primary driver of tissue fibrosis and contributes to the immunosuppressive environment in many cancers. Modern therapeutic approaches focus on selectively inhibiting the activation of specific latent TGF-beta isoforms to avoid the systemic toxicities associated with broad TGF-beta receptor blockade (Scholar Rock, 2023). Drugs like SRK-181 and ABBV-151 are designed to bind the latent complex and prevent the release of active TGF-beta in the tumor microenvironment or fibrotic tissues.

Other names

Small latent complexLarge latent complexSLCLLCpro-TGF-betaLAP-TGF-beta complexLatent TGF-beta1 complex

Selective inhibition of the activation of latent TGF-beta by preventing the release of the mature growth factor from the latency-associated peptide (LAP) or by blocking integrin-mediated activation.