Abstract:
:The Eph receptor tyrosine kinase family is regulated by autophosphorylation within the juxtamembrane region and the kinase activation segment. We have solved the X-ray crystal structure to 1.9 A resolution of an autoinhibited, unphosphorylated form of EphB2 comprised of the juxtamembrane region and the kinase domain. The structure, supported by mutagenesis data, reveals that the juxtamembrane segment adopts a helical conformation that distorts the small lobe of the kinase domain, and blocks the activation segment from attaining an activated conformation. Phosphorylation of conserved juxtamembrane tyrosines would relieve this autoinhibition by disturbing the association of the juxtamembrane segment with the kinase domain, while liberating phosphotyrosine sites for binding SH2 domains of target proteins. We propose that the autoinhibitory mechanism employed by EphB2 is a more general device through which receptor tyrosine kinases are controlled.
journal_name
Celljournal_title
Cellauthors
Wybenga-Groot LE,Baskin B,Ong SH,Tong J,Pawson T,Sicheri Fdoi
10.1016/s0092-8674(01)00496-2subject
Has Abstractpub_date
2001-09-21 00:00:00pages
745-57issue
6eissn
0092-8674issn
1097-4172pii
S0092-8674(01)00496-2journal_volume
106pub_type
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