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Ras proteins signal to a number of distinct pathways by interacting with diverse effectors. Studies of ras/effector interactions have focused on three classes, Raf kinases, ral guanylnucleotide-exchange factors, and phosphatidylinositol-3-kinases. Here we describe ras interactions with another effector, the recently identified phospholipase C epsilon (PLCepsilon). We solved structures of PLCepsilon RA domains (RA1 and RA2) by NMR and the structure of the RA2/ras complex by X-ray crystallography. Although the similarity between ubiquitin-like folds of RA1 and RA2 proves that they are homologs, only RA2 can bind ras. Some of the features of the RA2/ras interface are unique to PLCepsilon, while the ability to make contacts with both switch I and II regions of ras is shared only with phosphatidylinositol-3-kinase. Studies of PLCepsilon regulation suggest that, in a cellular context, the RA2 domain, in a mode specific to PLCepsilon, has a role in membrane targeting with further regulatory impact on PLC activity.

Original publication

DOI

10.1016/j.molcel.2006.01.008

Type

Journal article

Journal

Mol Cell

Publication Date

17/02/2006

Volume

21

Pages

495 - 507

Keywords

Amino Acid Sequence, Animals, Cell Line, Crystallography, X-Ray, Enzyme Activation, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Magnetic Resonance, Biomolecular, Phosphoinositide Phospholipase C, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Recombinant Fusion Proteins, Sequence Alignment, Signal Transduction, Thermodynamics, Type C Phospholipases, ras Proteins