Question

Which of the signaling receptors are generally activated by dimerization induced by binding to two sites on their ligand?

Answer 1

ANSWER

RECEPTOR WHICH ARE ACTIVATED BY DIMERIZATION INCLUDE

1. Receptor Tyrosine Kinase (RTK): Contains intrinsic tyrosine kinase activity (EGFR, VEGFR). Growth factors such as insulin, epidermal growth factor (EGF), and platelet-derived growth factor bind to the extracellular domains of transmembrane receptors that have tyrosine kinase domains present within their intracellular domains.The receptor tyrosine kinase is monomeric and enzymatically inactive in the absence of the growth factor. The binding of EGF to the extracellular domain causes the receptor to dimerize and undergo cross-phosphorylation and activation.
2. Receptor Serine/Threonine Kinase: Contains intrinsic serine/threonine kinase activity (TGF-βR)-Receptor serine/threonine kinases ( RSKs) are transmembrane proteins of the plasma membrane and are characterized by extracellular ligand‐binding domains and cytoplasmic kinase domains.The serine/threonine kinase receptors are typified by the receptors for transforming growth factor β (TGFβ), a dimeric ligand that exerts its effects through receptors composed of two different subunits designated type I and type II. Each possesses serine/threonine kinase activity. Both classes of receptor protomers are required for mediating the signaling response to ligand binding. The type II TGFβ receptor (TβR-II) exists as a constitutively active dimer and is responsible for the initial interaction with TGFβ, as the type I receptor (TβR-I) cannot bind TGFβ in the absence of TβR-II.
3. CYTOKINE RECEPTOR:Cytokine receptors activate many signaling pathways generally by means of phosphotyrosine residues, which are recognized by SH2 domains on the signaling molecules. The STATs contain a carboxy-terminal SH2 domain, an SH3-like domain and several conserved amino-terminal regions, and a conserved region in the middle of the protein that binds DNA. Tyrosine phosphorylation of a carboxy-terminal site mediates homo- or heterodimerization through the SH2 domains, triggering movement to the nucleus and DNA binding.A native un-liganded receptor in complex with a JAK is in a catalytically inactive latent state. Receptor dimerization/oligomerization due to ligand binding results in the juxtapositioning of the JAKs, which are in the vicinity through either homo- or heterodimeric interactions. The recruitment of JAKs appears to result in their phosphorylation, either via autophosphorylation and/or cross phosphorylation by other JAKs or via other families of tyrosine kinases. This activation is presumed to result in increased JAK activity. Activated JAKs then phosphorylate receptors on target tyrosine sites. The phosphotyrosine sites on the receptors can then serve as docking sites that allow the binding of other SH2-domain containing signaling molecules such as STATs, Src-kinases, protein phosphatases and other adaptor signaling proteins such as Shc, Grb2 and phosphatidylinositol 3-kinase (PI3K).