Structural highlights
Function
[SH2D3_HUMAN] Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity). [BCAR1_HUMAN] Docking protein which plays a central coordinating role for tyrosine kinase-based signaling related to cell adhesion. Implicated in induction of cell migration. Overexpression confers antiestrogen resistance on breast cancer cells.[1] [2]
Publication Abstract from PubMed
Members of the novel SH2-containing protein (NSP) and Crk-associated substrate (Cas) protein families form multidomain signaling platforms that mediate cell migration and invasion through a collection of distinct signaling motifs. Members of each family interact via their respective C-terminal domains, but the mechanism of this association has remained enigmatic. Here we present the crystal structures of the C-terminal domain from the NSP protein BCAR3 and the complex of NSP3 with p130Cas. BCAR3 adopts the Cdc25-homology fold of Ras GTPase exchange factors, but it has a 'closed' conformation incapable of enzymatic activity. The structure of the NSP3-p130Cas complex reveals that this closed conformation is instrumental for interaction of NSP proteins with a focal adhesion-targeting domain present in Cas proteins. This enzyme-to-adaptor conversion enables high-affinity, yet promiscuous, interactions between NSP and Cas proteins and represents an unprecedented mechanistic paradigm linking cellular signaling networks.
NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.,Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ Nat Struct Mol Biol. 2011 Nov 13. doi: 10.1038/nsmb.2152. PMID:22081014[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abassi YA, Rehn M, Ekman N, Alitalo K, Vuori K. p130Cas Couples the tyrosine kinase Bmx/Etk with regulation of the actin cytoskeleton and cell migration. J Biol Chem. 2003 Sep 12;278(37):35636-43. Epub 2003 Jun 28. PMID:12832404 doi:http://dx.doi.org/10.1074/jbc.M306438200
- ↑ Modzelewska K, Newman LP, Desai R, Keely PJ. Ack1 mediates Cdc42-dependent cell migration and signaling to p130Cas. J Biol Chem. 2006 Dec 8;281(49):37527-35. Epub 2006 Oct 12. PMID:17038317 doi:10.1074/jbc.M604342200
- ↑ Mace PD, Wallez Y, Dobaczewska MK, Lee JJ, Robinson H, Pasquale EB, Riedl SJ. NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling. Nat Struct Mol Biol. 2011 Nov 13. doi: 10.1038/nsmb.2152. PMID:22081014 doi:10.1038/nsmb.2152
