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2gs2

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{{STRUCTURE_2gs2| PDB=2gs2 | SCENE= }}
{{STRUCTURE_2gs2| PDB=2gs2 | SCENE= }}
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'''Crystal Structure of the active EGFR kinase domain'''
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===Crystal Structure of the active EGFR kinase domain===
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==Overview==
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The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization.
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{{ABSTRACT_PUBMED_16777603}}
==Disease==
==Disease==
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[[Category: Egfr]]
[[Category: Egfr]]
[[Category: Kinase]]
[[Category: Kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 04:54:10 2008''

Revision as of 01:54, 29 July 2008

Image:2gs2.png

Template:STRUCTURE 2gs2

Contents

Crystal Structure of the active EGFR kinase domain

Template:ABSTRACT PUBMED 16777603

Disease

Known disease associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, susceptibility to OMIM:[131550]

About this Structure

2GS2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor., Zhang X, Gureasko J, Shen K, Cole PA, Kuriyan J, Cell. 2006 Jun 16;125(6):1137-49. PMID:16777603

Page seeded by OCA on Tue Jul 29 04:54:10 2008

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