Ligand recognition and homophilic interactions in Tyro3 - Structural insights into the Axl/Tyro3 receptor tyrosine kinase family
(2004) In Journal of Biological Chemistry 279(8). p.6952-6958- Abstract
- The receptor Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases. Members of this family play essential roles in spermatogenesis, immunoregulation, and phagocytosis. Gas6, the product of growth arrest-specific gene, activates the kinase activity of all three receptors. Here, we report the first biochemical and structural characterization of a member of this family, namely of a fragment spanning the two N-terminal Ig domains of the extracellular part of human Tyro3. Its ligand binding specificity profile is identical to the activation profile of the native receptor. The 1.95-Angstrom crystal structure suggests a common ligand-binding site in this receptor family located at the interface of the Ig domains... (More)
- The receptor Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases. Members of this family play essential roles in spermatogenesis, immunoregulation, and phagocytosis. Gas6, the product of growth arrest-specific gene, activates the kinase activity of all three receptors. Here, we report the first biochemical and structural characterization of a member of this family, namely of a fragment spanning the two N-terminal Ig domains of the extracellular part of human Tyro3. Its ligand binding specificity profile is identical to the activation profile of the native receptor. The 1.95-Angstrom crystal structure suggests a common ligand-binding site in this receptor family located at the interface of the Ig domains and unusually rich in cis-prolines. Furthermore, both in the crystal and in solution we observed the ligand-independent dimerization of the receptor fragment. This homophilic interaction emphasizes previous functional reports, which hinted that in addition to signal transduction, members of this family of receptors might participate in cell adhesion. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/287095
- author
- Heiring, C ; Dahlbäck, Björn LU and Muller, YA
- organization
- publishing date
- 2004
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 279
- issue
- 8
- pages
- 6952 - 6958
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000188969200090
- pmid:14623883
- scopus:1342346567
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M311750200
- language
- English
- LU publication?
- yes
- id
- 0ec89493-467c-4a99-83ee-94247af04a12 (old id 287095)
- date added to LUP
- 2016-04-01 11:52:13
- date last changed
- 2022-04-28 21:17:34
@article{0ec89493-467c-4a99-83ee-94247af04a12,
abstract = {{The receptor Tyro3 together with Axl and Mer form the Axl/Tyro3 family of receptor tyrosine kinases. Members of this family play essential roles in spermatogenesis, immunoregulation, and phagocytosis. Gas6, the product of growth arrest-specific gene, activates the kinase activity of all three receptors. Here, we report the first biochemical and structural characterization of a member of this family, namely of a fragment spanning the two N-terminal Ig domains of the extracellular part of human Tyro3. Its ligand binding specificity profile is identical to the activation profile of the native receptor. The 1.95-Angstrom crystal structure suggests a common ligand-binding site in this receptor family located at the interface of the Ig domains and unusually rich in cis-prolines. Furthermore, both in the crystal and in solution we observed the ligand-independent dimerization of the receptor fragment. This homophilic interaction emphasizes previous functional reports, which hinted that in addition to signal transduction, members of this family of receptors might participate in cell adhesion.}},
author = {{Heiring, C and Dahlbäck, Björn and Muller, YA}},
issn = {{1083-351X}},
language = {{eng}},
number = {{8}},
pages = {{6952--6958}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Ligand recognition and homophilic interactions in Tyro3 - Structural insights into the Axl/Tyro3 receptor tyrosine kinase family}},
url = {{http://dx.doi.org/10.1074/jbc.M311750200}},
doi = {{10.1074/jbc.M311750200}},
volume = {{279}},
year = {{2004}},
}