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Allosteric Mechanisms in Receptor Tyrosine Kinase Activation
Author(s) -
Kuriyan John
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.313.1
Subject(s) - receptor tyrosine kinase , allosteric regulation , tyrosine kinase , microbiology and biotechnology , ror1 , epidermal growth factor receptor , proto oncogene tyrosine protein kinase src , transmembrane protein , kinase , chemistry , guanine nucleotide exchange factor , tropomyosin receptor kinase c , signal transduction , biochemistry , biology , platelet derived growth factor receptor , receptor , growth factor
The control mechanisms that govern the response of receptor tyrosine kinases to input signals are multi‐layered and complex. Our studies on the epidermal growth factor receptor (EGFR) and the downstream Ras‐specific guanine exchange factor (Son of Sevenless, SOS) will be presented. For EGFR, we have defined a specific asymmetric interaction between kinase domains that is necessary for activity. Potential mechanisms that couple this activating dimerization to the transmembrane segments of the receptor will be discussed. The activation of SOS by EGFR and other tyrosine kinases involves the recruitment of SOS to the membrane, where it encounters Ras. We have uncovered an unexpected mechanism in which Ras itself is capable of tethering SOS to membranes in a way that makes SOS responsive to the presence of PIP2 in the membrane, as well as the surface density of Ras. The implications of these finding for the activation of Ras will be discussed.