1nql: Difference between revisions

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==Overview==

Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER), family receptor tyrosine kinases (RTKs), which regulate cell growth and, differentiation and are implicated in many human cancers. EGF activates, its receptor by inducing dimerization of the 621 amino acid EGF receptor, extracellular region. We describe the 2.8 A resolution crystal structure, of this entire extracellular region (sEGFR) in an unactivated state. The, structure reveals an autoinhibited configuration, where the dimerization, interface recently identified in activated sEGFR structures is completely, occluded by intramolecular interactions. To activate the receptor, EGF, binding must promote a large domain rearrangement that exposes this, dimerization interface. This contrasts starkly with other RTK activation, mechanisms and suggests new approaches for designing ErbB receptor, antagonists.

Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER) family receptor tyrosine kinases (RTKs), which regulate cell growth and differentiation and are implicated in many human cancers. EGF activates its receptor by inducing dimerization of the 621 amino acid EGF receptor extracellular region. We describe the 2.8 A resolution crystal structure of this entire extracellular region (sEGFR) in an unactivated state. The structure reveals an autoinhibited configuration, where the dimerization interface recently identified in activated sEGFR structures is completely occluded by intramolecular interactions. To activate the receptor, EGF binding must promote a large domain rearrangement that exposes this dimerization interface. This contrasts starkly with other RTK activation mechanisms and suggests new approaches for designing ErbB receptor antagonists.

==Disease==

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[[Category: Homo sapiens]]

[[Category: Protein complex]]

[[Category: Ferguson, K.M.]]

[[Category: Ferguson, K M.]]

[[Category: Lemmon, M.A.]]

[[Category: Lemmon, M A.]]

[[Category: NAG]]

[[Category: auto-inhibition]]

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[[Category: tyrosine kinase]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Fri~~ Feb ~~15 16~~:30:30 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:08:58 2008''

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@@ Line 4: / Line 4: @@
 ==Overview==
-Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER), family receptor tyrosine kinases (RTKs), which regulate cell growth and, differentiation and are implicated in many human cancers. EGF activates, its receptor by inducing dimerization of the 621 amino acid EGF receptor, extracellular region. We describe the 2.8 A resolution crystal structure, of this entire extracellular region (sEGFR) in an unactivated state. The, structure reveals an autoinhibited configuration, where the dimerization, interface recently identified in activated sEGFR structures is completely, occluded by intramolecular interactions. To activate the receptor, EGF, binding must promote a large domain rearrangement that exposes this, dimerization interface. This contrasts starkly with other RTK activation, mechanisms and suggests new approaches for designing ErbB receptor, antagonists.
+Epidermal growth factor (EGF) receptor is the prototype of the ErbB (HER) family receptor tyrosine kinases (RTKs), which regulate cell growth and differentiation and are implicated in many human cancers. EGF activates its receptor by inducing dimerization of the 621 amino acid EGF receptor extracellular region. We describe the 2.8 A resolution crystal structure of this entire extracellular region (sEGFR) in an unactivated state. The structure reveals an autoinhibited configuration, where the dimerization interface recently identified in activated sEGFR structures is completely occluded by intramolecular interactions. To activate the receptor, EGF binding must promote a large domain rearrangement that exposes this dimerization interface. This contrasts starkly with other RTK activation mechanisms and suggests new approaches for designing ErbB receptor antagonists.
 ==Disease==
@@ Line 16: / Line 16: @@
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
-[[Category: Ferguson, K.M.]]
+[[Category: Ferguson, K M.]]
-[[Category: Lemmon, M.A.]]
+[[Category: Lemmon, M A.]]
 [[Category: NAG]]
 [[Category: auto-inhibition]]
@@ Line 26: / Line 26: @@
 [[Category: tyrosine kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:30:30 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:08:58 2008''