TGF-β cytokines are generated by cleavage of the dimeric C-terminal domain of a biosynthetic precursor in the Golgi. The mature cytokine remains sequestered by non-covalent binding to the N-terminal domain of the precursor, or latency-associated peptide (LAP). LAP in this complex becomes disulfide-linked to one of three latent TGF-β binding protein (LTBP) isoforms, and the complex is tethered deposited to the extracellular matrix (ECM) after secretion. Alternatively, in the indicated cell types, LAP in the TGF-β complex becomes disulfide-linked to the membrane-anchored proteins GARP or LRRC33 and retained on the cell surface.
