The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions

NIK is a component of the EGF/heregulin receptor signaling complexes

“…The SH2 domain of the Grb7 family is responsible for interaction with the majority of identified Grb7-interacting proteins, such as the EGF receptor family members, Shc, Raf, Tek/Tie2, and FAK, among others (Han et al, 2001). It has been shown that the PR domain of Grb7 family members interacts with c-Abl and Tankyrase (Frantz et al, 1997;Han et al, 2001;Lyons et al, 2001). Proteins that interact with the large central GM domain of the Grb7 family members are not known.…”

“…Unlike Grb2, which contains an SH2 domain flanked by two SH3 domains, the Grb7 family members contain an N-terminal proline-rich (PR) region, a central GM region that is homologous with the C. elegans protein Mig10, and a C-terminal SH2 domain (Daly, 1998;Han et al, 2001). The SH2 domain of the Grb7 family is responsible for interaction with the majority of identified Grb7-interacting proteins, such as the EGF receptor family members, Shc, Raf, Tek/Tie2, and FAK, among others (Han et al, 2001). It has been shown that the PR domain of Grb7 family members interacts with c-Abl and Tankyrase (Frantz et al, 1997;Han et al, 2001;Lyons et al, 2001).…”

“…The Grb7 family consists of Grb7, Grb10, and Grb14, which do not have intrinsic enzymatic activity and signal through their interaction with downstream proteins (Daly, 1998;Han et al, 2001). Unlike Grb2, which contains an SH2 domain flanked by two SH3 domains, the Grb7 family members contain an N-terminal proline-rich (PR) region, a central GM region that is homologous with the C. elegans protein Mig10, and a C-terminal SH2 domain (Daly, 1998;Han et al, 2001). The SH2 domain of the Grb7 family is responsible for interaction with the majority of identified Grb7-interacting proteins, such as the EGF receptor family members, Shc, Raf, Tek/Tie2, and FAK, among others (Han et al, 2001).…”

Grb7 expression and cellular migration in chronic lymphocytic leukemia: a comparative study of early and advanced stage disease

“…5 The noncatalytic adaptor protein Grb7 has been related to the regulation of integrin-mediated cell migration, and to solid tumor progression and invasion. 6 Adaptor proteins function to mediate the coupling of multiple cell surface receptors to downstream signaling pathways, and thus are positioned to regulate cell signaling in a spatial and temporal way. Abnormal expression of adaptor proteins leads to significant derangements in intracellular signaling pathways and facilitates malignant processes.…”

HapMap-based study of the 17q21 ERBB2 amplicon in susceptibility to breast cancer

“…Overexpression of PNMT results in suppression of circulating leptin levels -a potent regulator of body weight -in transgenic mice (Bottner et al, 2000;Harvey and Ashford, 2003). CAB2 is a human homologue of the yeast COS16 gene required for the repair of DNA double-strand breaks (Nezu et al, 2002) and GRB7 regulates cell migration through its involvement in cell signalling pathways (Han et al, 2001). Finally, ZNFN1A3 appears to function as a tumour suppressor since its downregulation in the mouse leads to leukaemias and lymphomas (Rebollo and Schmitt, 2003).…”