1. Merlin and ERM protein domain organization and phosphoregulation.
Merlin and ERM protein domain organization and phosphoregulation. (A) Merlin and other canonical ERM proteins have similar domain organizations consisting of an amino‐terminal (N‐term) FERM domain that is divided into three subdomains, an α‐helical coiled‐coil domain and a carboxy‐terminal (C‐term) hydrophilic tail. Canonical ERM proteins contain an actin‐binding C‐terminal ERM‐associated domain (C‐ERMAD; pink), whereas Merlin does not. It also has an extended N‐terminal motif (green) unique among ERM proteins, illustrating its divergent structure with respect to other ERM proteins. Merlin phosphorylation sites are indicated. (B) Canonical ERM proteins are maintained in an inactive state by intramolecular interaction between the C‐terminal tail and FERM domain. Phosphorylation of a C‐terminal threonine by Rho kinase—which might be aided by ERM protein recruitment to membrane regions rich in phosphatidylinositol 4,5‐bisphosphate—activates the protein by disrupting the head‐to‐tail interaction. (C) Conversely, Merlin's dephosphorylated and closed form is active and functions in tumour suppression and contact inhibition. Phosphorylation by PAK and PKA at Ser 518 renders the protein inactive in its putatively open form. ERM, Ezrin/Radixin/Moesin; FERM, 4.1 protein/Ezrin/Radixin/Moesin; MYPT1, myosin phosphatase targeting subunit 1; PAK, p21‐activated kinase; PKA, protein kinase A; PIP2, phosphatidylinositol 4,5‐bisphosphate; RhoK, Ras homologue gene family, member K.
Wei Li et al. EMBO Rep. 2012;13:
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