TY - JOUR
T1 - Receptor tyrosine kinase structure and function in health and disease
AU - Karpov, Oleg A.
AU - Fearnley, Gareth W.
AU - Smith, Gina A.
AU - Kankanala, Jayakanth
AU - McPherson, Michael J.
AU - Tomlinson, Darren C.
AU - Harrison, Michael A.
AU - Ponnambalam, Sreenivasan
N1 - Publisher Copyright:
© 2015, Sreenivasan Ponnambalam, et al.
PY - 2015
Y1 - 2015
N2 - Receptor tyrosine kinases (RTKs) are membrane proteins that control the flow of information through signal transduction pathways, impacting on different aspects of cell function. RTKs are characterized by a ligand-binding ectodomain, a single transmembrane a-helix, a cytosolic region comprising juxtamembrane and kinase domains followed by a flexible C-terminal tail. Somatic and germline RTK mutations can induce aberrant signal transduction to give rise to cardiovascular, developmental and oncogenic abnormalities. RTK overexpression occurs in certain cancers, correlating signal strength and disease incidence. Diverse RTK activation and signal transduction mechanisms are employed by cells during commitment to health or disease. Small molecule inhibitors are one means to target RTK function in disease initiation and progression. This review considers RTK structure, activation, and signal transduction and evaluates biological relevance to therapeutics and clinical outcomes.
AB - Receptor tyrosine kinases (RTKs) are membrane proteins that control the flow of information through signal transduction pathways, impacting on different aspects of cell function. RTKs are characterized by a ligand-binding ectodomain, a single transmembrane a-helix, a cytosolic region comprising juxtamembrane and kinase domains followed by a flexible C-terminal tail. Somatic and germline RTK mutations can induce aberrant signal transduction to give rise to cardiovascular, developmental and oncogenic abnormalities. RTK overexpression occurs in certain cancers, correlating signal strength and disease incidence. Diverse RTK activation and signal transduction mechanisms are employed by cells during commitment to health or disease. Small molecule inhibitors are one means to target RTK function in disease initiation and progression. This review considers RTK structure, activation, and signal transduction and evaluates biological relevance to therapeutics and clinical outcomes.
KW - Cancer
KW - Development
KW - Disease
KW - Membrane trafficking
KW - Phosphorylation
KW - Proteolysis
KW - Receptor tyrosine kinase
KW - Signal transduction
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U2 - 10.3934/biophy.2015.4.476
DO - 10.3934/biophy.2015.4.476
M3 - Review article
AN - SCOPUS:85018195571
SN - 2377-9098
VL - 2
SP - 476
EP - 502
JO - AIMS Biophysics
JF - AIMS Biophysics
IS - 4
ER -