Examples of mechanisms that cells can use for the in vivo for the control of effective ligand concentrations and receptor expression (and thus the level of receptor-ligand complex activation).

(1) Preventing or diminishing ligand/receptor complex internalization through interactions between extracellular matrix (shown) or cell-surface bound ligands; (2) autocrine ligand secretion; (3) interactions with proteins secreted by other cells (either locally or systemically); (4) ligand interactions with agonistic or antagonistic soluble receptors (shown) or nonreceptor cytokine binding proteins (eg, uromodulin); (5) receptor internalization/synthesis; and (6) proteolytic cleavage of surface-bound receptors (shown) and/or ligands. Each of these mechanisms may determine whether a particular (threshold) level of receptor ligand activation is achieved. See text for further discussion.