Figure 1

Mode of action of ADAMs in the activation of EGFR/HER receptor signalling. ADAMs (primarily ADAM10 and ADAM17) are involved in proteolytic ectodomain shedding of membrane bound ligands. The released ligands (for example, EGF, HB-EGF, TGFα, heregulins) are free to bind to and activate EGFR, HER3 and HER4. Following receptor dimerisation (though HER3 has weak tyrosine kinase activity, its preferred dimerization partner is HER2), downstream signalling through many pathways is activated, including MAPK, PI3K and JAK/STAT.