echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Biochemistry News > Biotechnology News > Signaling by Growth Factor Receptors

    Signaling by Growth Factor Receptors

    • Last Update: 2020-12-27
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Growth factor receptors (GFRs) represent a subset of a large class of proteins that serve as extracellular environment sensors of the cell. They are single transmembrane proteins with an extracellular ligand-binding domain (LBD) and an intracellular tyrosine kinase domain (
    1
    ,
    2
    ). Individual GFRs are expressed in specific cell types and their expression is highly regulated during development. In the case of polarized cells, newly synthesized receptors are targeted to specific faces of the cell through the exocytic pathway. The mechanism of signal transduction by ligand-activated GFRs is schematically depicted in Fig. 1 . Oligomerization induced by ligand binding results in the allosteric activation of the intracellular tyrosine kinase (
    3
    ). A variety of cellular proteins are phosphorylated by the activated kinase, including the receptors themselves (
    4
    ). The phosphorylated tyrosine residues serve as docking sites for various signal transducers containing a phosphotyrosine-binding domain or an Src homology 2 (SH2) domain. Thus, a multiprotein signaling complex is assembled in the vicinity of the receptor. The ligand determines which receptors are activated, whereas the receptors involved dictate the type of proteins recruited to the signaling complex, which in turn determines the nature of the downstream signaling cascade. Although a large number of GFR families have been identified, their mode of activation, orchestration of signaling, and downregulation are modular (
    5
    ).Fig. 1.
    Schematic representation of receptor activation and downregulation. Ligand-induced dimerization leads to auto- and transphosphorylation of tyrosine residues in the C-terminus of the receptor, which serve as docking sites for cytoplasmic proteins containing a phosphotyrosine binding domain. Note that some of the recruited proteins also serve as substrates of the receptor. Only a few of the pathways activated by the receptor are depicted here. Many downstream effectors are subsequently activated, and the signal is carried across the nuclear membrane, culminating in nascent gene expression and cell-fate determination. The c-Cbl•E2 complex may interact with the receptor already at the cell surface, and it mediates receptor ubiquitination. Ubiquitinated receptors are then sorted into clathrin-coated pits and endocytosed. The fate of the receptor in the early endosome may be determined by the extent of ubiquitination: de-ubiquitinated receptors may be recycled back to the plasma membrane while extensively ubiquitinated receptors are apparently carried to multivesicular bodies and eventually to the lysosome, where they are degraded.
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.