Structural highlights
Function
ANS1A_MOUSE Regulator of different signaling pathways. Regulates EPHA8 receptor tyrosine kinase signaling to control cell migration and neurite retraction.[1] EPHA6_MOUSE Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling (By similarity).
Publication Abstract from PubMed
The Eph receptor tyrosine kinase (RTK) family is the largest subfamily of RTKs playing critical roles in many developmental processes such as tissue patterning, neurogenesis and neuronal circuit formation, angiogenesis, etc. How the 14 Eph proteins, via their highly similar cytoplasmic domains, can transmit diverse and sometimes opposite cellular signals upon engaging ephrins is a major unresolved question. Here we systematically investigated the bindings of each SAM domain of Eph receptors to the SAM domains from SHIP2 and Odin, and uncover a highly specific SAM-SAM interaction-mediated cytoplasmic Eph-effector binding pattern. Comparative X-ray crystallographic studies of several SAM-SAM heterodimer complexes, together with biochemical and cell biology experiments, not only revealed the exquisite specificity code governing Eph/effector interactions but also allowed us to identify SAMD5 as a new Eph binding partner. Finally, these Eph/effector SAM heterodimer structures can explain many Eph SAM mutations identified in patients suffering from cancers and other diseases.
Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions.,Wang Y, Shang Y, Li J, Chen W, Li G, Wan J, Liu W, Zhang M Elife. 2018 May 11;7. pii: 35677. doi: 10.7554/eLife.35677. PMID:29749928[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shin J, Gu C, Park E, Park S. Identification of phosphotyrosine binding domain-containing proteins as novel downstream targets of the EphA8 signaling function. Mol Cell Biol. 2007 Dec;27(23):8113-26. Epub 2007 Sep 17. PMID:17875921 doi:http://dx.doi.org/MCB.00794-07
- ↑ Wang Y, Shang Y, Li J, Chen W, Li G, Wan J, Liu W, Zhang M. Specific Eph receptor-cytoplasmic effector signaling mediated by SAM-SAM domain interactions. Elife. 2018 May 11;7. pii: 35677. doi: 10.7554/eLife.35677. PMID:29749928 doi:http://dx.doi.org/10.7554/eLife.35677
