Alternatively, the EPH:ephrin (EPH:EFN) interaction can be broken by proteolytic cleavage of the EPH receptors by matrix metalloproteinases (MMPs) and gamma-secretase. Ethell and his group showed that the EPHB2 receptor is cleaved by the secreted MMPs MMP-2 and MMP-9, and this cleavage is induced by EFNB:EPHB receptor interaction. EPHB2 receptor is initially cleaved within the fibronectin (FN) type III domain or between residues 543 and 544 (mouse EPHB2) at the cell surface by MMPs to produce a long fragment that is released to the extracellular space and a membrane bound C-terminal fragment (Ethell et al. 2007, Litterst et al. 2007).