Dataset Information


Structure of the SOCS4-ElonginB/C complex reveals a distinct SOCS box interface and the molecular basis for SOCS-dependent EGFR degradation.

ABSTRACT: Tyrosine kinase signaling is tightly controlled by negative feedback inhibitors including suppressors of cytokine signaling (SOCS). SOCS assemble as SH2 domain substrate recognition modules in ElonginB/C-cullin ubiquitin ligases. In accordance, SOCS4 reduces STAT3 signaling from EGFR through increased receptor degradation. Variable C-termini in SOCS4-SOCS7 exclude these family members from a SOCS2-type domain arrangement in which a strictly conserved C terminus determines domain packing. The structure of the SOCS4-ElonginC-ElonginB complex reveals a distinct SOCS structural class. The N-terminal ESS helix functionally replaces the CIS/SOCS1-SOCS3 family C terminus in a distinct SH2-SOCS box interface that facilitates further interdomain packing between the extended N- and C-terminal regions characteristic for this subfamily. Using peptide arrays and calorimetry the STAT3 site in EGFR (pY(1092)) was identified as a high affinity SOCS4 substrate (K(D) = 0.5 microM) revealing a mechanism for EGFR degradation. SOCS4 also bound JAK2 and KIT with low micromolar affinity, whereas SOCS2 was specific for GH-receptor.


PROVIDER: S-EPMC2225448 | BioStudies | 2007-01-01

REPOSITORIES: biostudies

Similar Datasets

2006-01-01 | S-EPMC1472497 | BioStudies
2019-01-01 | S-EPMC6368001 | BioStudies
2011-01-01 | S-EPMC3937865 | BioStudies
2015-01-01 | S-EPMC4678202 | BioStudies
1000-01-01 | S-EPMC1171132 | BioStudies
2002-01-01 | S-EPMC133908 | BioStudies
2013-01-01 | S-EPMC3430812 | BioStudies
2017-01-01 | S-EPMC5589800 | BioStudies
2013-01-01 | S-EPMC3843819 | BioStudies
1998-01-01 | S-EPMC18144 | BioStudies