【摘 要】
：
Constitutive receptor tyrosine kinase phosphorylation requires regulation of kinase and phosphatase activity to prevent aberrant signal transduction.A dynam
【机 构】
：
DepartmentofStructural&MolecularBiology,UniversityCollegeLondon,GowerStreet,London,WC1E6BT,UK
【出 处】
：
3rd International Conference on Fibroblast Growth Factors (F
论文部分内容阅读
Constitutive receptor tyrosine kinase phosphorylation requires regulation of kinase and phosphatase activity to prevent aberrant signal transduction.A dynamic mechanism is described in which the adaptor protein Grb2 controls FGFR2 signaling by regulating receptor kinase and Shp2 phosphatase activity in the absence of extracellular stimulation.FGFR2 cycles between its kinase active, partially phosphorylated, non-signaling state and its Shp2-dephosphorylated state.Concurrently Shp2 cycles between its inactive, dephosphorylated form and its active, FGFR2-phosphorylated form.Both reciprocal activities of FGFR2 and Shp2 are inhibited by binding of Grb2 to the receptor.Phosphorylation of Grb2 by FGFR2 abrogates its binding to receptor, resulting in upregulation of both kinase and phosphatase activity.Dephosphorylation of Grb2 by Shp2 rescues the FGFR2-Grb2 complex and re-imposes control.This cycling of enzymatic activity results in a homeostatic, signaling-incompetent state.Growth factor binding perturbs this background cycling, promoting FGFR2 kinase activity, Grb2 dissociation and downstream signaling.Grb2 therefore exerts constitutive control over the mutually dependent activities of FGFR2 and Shp2.
其他文献
Urogynecology is in a major transition in the United States, after a decade of rapid growth, with the advent of transvaginal and transobturator slings, sing
Being diagnosed with breast cancer is a traumatic experience that can elevate levels of distress and cause depletion of coping resources in many of the dise
In The aim of this study, there were two aims.One aim was to clarify the perceptions of both infertile women accessing support services from local governmen
Intimate partner abuse (IPA) is a common hidden problem for one in ten women attending general practice.IPA is the leading cause of death and disability for
Although Cesarean birth is identified as a persistent barrier to breastfeeding, operative delivery rates have risen at an alarming rate worldwide.Consequent
Despite overall diversity of the FGF signal transduction family in number of activating ligands (FGFs) and tyrosine kinase receptor (FGFR) variants and its
Receptor tyrosine kinases (RTKs) play fundamental roles in human biology and pathology.In the monomeric RTK, the tyrosine kinase domain is repressed by a va
The ciliated mechanosensory cells of the inner ear, the hair cells, are uniquely adapted to their task detecting sound and balance information.However their