Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain (Record no. 40450)

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fixed length control field 02774nam a2200253Ia 4500
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control field MX-MdCICY
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control field 20250625122511.0
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Transcribing agency CICY
090 ## - LOCALLY ASSIGNED LC-TYPE CALL NUMBER (OCLC); LOCAL CALL NUMBER (RLIN)
Classification number (OCLC) (R) ; Classification number, CALL (RLIN) (NR) B-6105
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245 10 - TITLE STATEMENT
Title Activation of preformed EGF receptor dimers by ligand-induced rotation of the transmembrane domain
490 0# - SERIES STATEMENT
Volume/sequential designation Journal of Molecular Biology , 311(5), p.1011-1026, 2001
520 3# - SUMMARY, ETC.
Summary, etc. The epidermal growth factor receptor plays crucial roles throughout the development of multicellular organisms, and inappropriate activation of the receptor is associated with neoplastic transformation of many cell types. The receptor is thought to be activated by ligand-induced homodimerisation. Here, however, we show by chemical cross-linking and sucrose density-gradient centrifugation that in the absence of bound ligand the receptor has an ability to form a dimer and exists as a preformed dimer on the cell surface. We also analysed the receptor dimerisation by inserting cysteine residues at strategic positions about the putative -helix axis of the extracellular juxtamembrane region. The mutant receptors spontaneously formed disulphide bridges and transformed NIH3T3 cells in the absence of ligand, depending upon the positions of the cysteine residue inserted. Kinetic analyses of the disulphide bonding indicate that EGF binding induces flexible rotation or twist of the juxtamembrane region of the receptor in the plane parallel with the lipid bilayer. The binding of an ATP competitor to the intracellular domain also induced similar flexible rotation of the juxtamembrane region. All the disulphide-bonded dimers had flexible ligand-binding domains with the same biphasic affinities for EGF as the wild-type. These results demonstrate that ligand binding to the flexible extracellular domains of the receptor dimer induce rotation or twist of the juxtamembrane regions, hence the transmembrane domains, and dissociate the dimeric, inactive form of the intracellular domains. The flexible rotation of the intracellular domains may be necessary for the intrinsic catalytic kinase to become accessible to the multiple tyrosine residues present in the regulatory domain and various substrates, and may be a common property of many cell-surface receptors, such as the insulin receptor.
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element CELL-SURFACE RECEPTOR
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element TRANSMEMBRANE SIGNALLING
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element CYSTEINE DISULPHIDE CROSS-LINKING
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element MOLECULAR MECHANISM
650 14 - SUBJECT ADDED ENTRY--TOPICAL TERM
Topical term or geographic name entry element MODEL
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Morikia, T.
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Maruyama, H.
700 12 - ADDED ENTRY--PERSONAL NAME
Personal name Maruyama, I.N.
856 40 - ELECTRONIC LOCATION AND ACCESS
Uniform Resource Identifier <a href="https://drive.google.com/file/d/1b92iLv5ua7HqSnNx6CkszV8jwywroYBe/view?usp=drivesdk">https://drive.google.com/file/d/1b92iLv5ua7HqSnNx6CkszV8jwywroYBe/view?usp=drivesdk</a>
Public note Para ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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Source of classification or shelving scheme Clasificación local
Koha item type Documentos solicitados
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  Clasificación local     Ref1 CICY CICY Documento préstamo interbibliotecario 25.06.2025   B-6105 25.06.2025 25.06.2025 Documentos solicitados