Adhesion

Integrins regulate GTP-Rac localized effector interactions through dissociation of Rho-GDI.Del Pozo, M. A. et al. Nat Cell Biol. 4, 232?239 (2002)

Integrin-mediated cell adhesion is required to translocate the small GTPase Rac to the plasma membrane, where it can interact with its effectors. In this study, the authors used fluorescence resonance energy transfer to show that Rac only interacts with its effectors at specific regions at the edges of cells. This was due to the ability of integrins to target Rac to these regions and to dissociate it from Rho·GDI, which binds to cytoplasmic Rac and blocks effector binding.

Sumoylation

Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity.Schmidt, D. & Müller, S. Proc. Natl Acad. Sci. USA 99, 2872?2877 (2002)

Like ubiquitylation, sumoylation requires an E1-activating enzyme and an E2-type conjugating enzyme, Ubc9. Until now, Ubc9 was also thought to be sufficient for substrate recognition, which, in the case of ubiquitylation, is carried out by E3 ligases. Now, however, Schmidt and Müller report that protein inhibitor of activated STAT (PIAS) proteins can function as specific SUMO ligases, in a similar manner to E3 ubiquitin ligases, and can mediate the sumoylation of p53 and c-Jun. PIAS-mediated sumoylation of p53 markedly repressed p53's transcriptional activity, indicating a role for the PIAS?SUMO pathway in transcriptional regulation.

Cell signalling

Cbl?CIN85?endophilin complex mediates ligand-induced downregulation of EGF receptors.Soubeyran, P. et al. Nature 416, 183?187 (2002)

The endophilin?CIN85?Cbl complex mediates ligand-dependent downregulation of c-Met.Petrelli, A. et al. Nature 416, 187?190 (2002)

The adaptor protein Cbl is involved in downregulating receptor-tyrosine kinases in response to ligand-induced activation by binding, through its Src-homology-2 (SH2) domain, to phosphorylated tyrosine residues. It then targets the receptors for ubiquitylation and subsequent degradation in lysosomes. But two new studies in Nature now show that Cbl also has a regulatory role in receptor internalization that is functionally separable from its ubiquitylation activity. Both research groups found that Cbl interacts, through its carboxyl terminus, with a complex that consists of endophilins ? components of clathrin-coated vesicles that mediate endocytosis ? and Cbl-interacting protein of 85 kDa, CIN85. The model proposed is that endophilin can alter the shape of the plasma membrane, thereby promoting membrane invagination, and that CIN85, an adaptor protein, might regulate receptor transport.