Cariou Bertrand, Bereziat Veronique, Moncoq Karine, Kasus-Jacobi Anne, Perdereau Dominique, Le Marcis Veronique, Burnol Anne-Francoise
Departement d'Endocrinologie, Institut Cochin INSERM U 567- CNRS UMR 8104-Universite Rene Descartes, 75014 Paris, France.
Front Biosci. 2004 May 1;9:1626-36. doi: 10.2741/1228.
Grb14 is the last described member of the Grb7 family of adaptors, containing Grb7, Grb10 and Grb14. These proteins share a series of conserved domains involved in protein-protein and protein-lipid interactions: an amino terminal proline-rich region, a C-terminal SH2 domain, and a central GM region containing a RA, a PH domain, and a newly described PIR (BPS) region. As shown for the other members of the Grb7/10/14 family, Grb14 binds to various receptor tyrosine kinases (RTKs) under ligand induction. This interaction involves the SH2 and PIR domains, and the respective participation of these domains is likely to be a determinant in the specificity of action of Grb14. At the present time, a role for this Grb14-RTK interaction was established only for insulin (IR) and FGF receptors (FGFR). Grb14, through its PIR, is an inhibitor of IR tyrosine kinase activity and thus of insulin effects. Grb14 also decreases FGF signaling, but more probably by interfering with cellular effectors downstream from the receptor. Only a few cytosolic partners of Grb14 are identified. One of them, the adaptor ZIP, allows phosphorylation of Grb14, and regulation of its inhibitory action on IR signaling. The identification of further proteins interacting with Grb14 is required to elucidate the biological role of this protein.
Grb14是衔接蛋白Grb7家族中最后被描述的成员，该家族还包括Grb7、Grb10和Grb14。这些蛋白质共享一系列参与蛋白质-蛋白质和蛋白质-脂质相互作用的保守结构域：一个富含脯氨酸的氨基末端区域、一个C末端SH2结构域以及一个包含RA、一个PH结构域和一个新描述的PIR（BPS）区域的中央GM区域。正如Grb7/10/14家族的其他成员所示，Grb14在配体诱导下与各种受体酪氨酸激酶（RTK）结合。这种相互作用涉及SH2和PIR结构域，这些结构域各自的参与可能是Grb14作用特异性的决定因素。目前，仅确定了Grb14与RTK相互作用在胰岛素（IR）和FGF受体（FGFR）方面的作用。Grb14通过其PIR是IR酪氨酸激酶活性的抑制剂，并因此是胰岛素作用的抑制剂。Grb14还会降低FGF信号传导，但更可能是通过干扰受体下游的细胞效应器来实现。仅鉴定出了少数Grb14的胞质结合伴侣。其中之一，衔接蛋白ZIP，可使Grb14磷酸化，并调节其对IR信号传导的抑制作用。需要鉴定与Grb14相互作用的更多蛋白质，以阐明该蛋白质的生物学作用。
