Structural highlights
Function
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] PTN12_HUMAN Dephosphorylates cellular tyrosine kinases, including PTK2B/PYK2, and thereby regulates signaling via PTK2B/PYK2.[3]
Publication Abstract from PubMed
CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5. We further expanded the knowledge of CAS SH3 ligand binding regulation by manipulating tyrosine 12 phosphorylation and confirmed the negative role of this phosphorylation on CAS SH3 ligand binding. Finally, by exploiting the newly identified binding requirements of the CAS SH3 domain, we predicted and experimentally verified two novel CAS SH3 binding partners, DOK7 and GLIS2.
Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners.,Gemperle J, Hexnerova R, Lepsik M, Tesina P, Dibus M, Novotny M, Brabek J, Veverka V, Rosel D Sci Rep. 2017 Aug 14;7(1):8057. doi: 10.1038/s41598-017-08303-4. PMID:28808245[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Sahu SN, Nunez S, Bai G, Gupta A. Interaction of Pyk2 and PTP-PEST with leupaxin in prostate cancer cells. Am J Physiol Cell Physiol. 2007 Jun;292(6):C2288-96. Epub 2007 Feb 28. PMID:17329398 doi:http://dx.doi.org/10.1152/ajpcell.00503.2006
- ↑ Gemperle J, Hexnerova R, Lepsik M, Tesina P, Dibus M, Novotny M, Brabek J, Veverka V, Rosel D. Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners. Sci Rep. 2017 Aug 14;7(1):8057. doi: 10.1038/s41598-017-08303-4. PMID:28808245 doi:http://dx.doi.org/10.1038/s41598-017-08303-4
