Grb7 in intracellular signaling and its role in cell regulation.
Grb7 is an adaptor molecule that mediates signal transduction from multiple cell surface receptors to various downstream signaling pathways. Grb7 and its related family member Grb10 and Grb14 share a conserved molecular architecture including an amino-terminal proline-rich region, a central segment termed the GM region (for Grb and Mig) which includes a PH domain and shares sequence homology with the Caenorhabditis elegans protein, Mig-10, and a carboxyl-terminal SH2 domain. Grb7/10/14 family proteins are phosphorylated on serine/threonine as well as tyrosine residues, although the functional significance of such phosphorylation is incompletely understood. Grb7/10/14 family proteins are mainly localized in the cytoplasm, but have been observed at the plasma membrane, focal contacts, or mitochondria under certain conditions. A large number of receptor tyrosine kinases and other signaling molecules can associate with Grb7/10/14 family proteins, mostly through the SH2 domains, although the functional consequences of such interactions have not been well characterized in most cases. Recent studies have suggested that various isoforms of Grb10 play important roles in mediating insulin/insulin-like growth factor regulation of cell proliferation and apoptosis, whereas Grb7 mediates signaling pathways from FAK and EphB1 receptor to regulate cell migration, which is also implicated in tumor progression. This review will discuss the current understanding of Grb7 mediated signal transduction pathways and their role in the regulation of various cellular functions.
Shen
Tang-Long
TL
Department of Molecular Medicine, Cornell University, Ithaca, New York 14853, USA.
Guan
Jun-Lin
JL
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D051382:GRB7 Adaptor Protein; D006801:Humans; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
C495955:GRB7 protein, human; D011506:Proteins; D051382:GRB7 Adaptor Protein