Many intracellular targets for receptor tyrosine kinases (RTKs) contain one or more SH2 (Src homology region 2) domains. These are conserved, noncatalytic domains that bind to short peptide sequences containing phosphotyrosine. After RTK activation, autophosphorylation occurs, and SH2 proteins bind to specific RTKs. Proteins containing SH2 domains are also thought to mediate other protein-protein interactions during signal transduction. Screening of a human breast epithelial cell cDNA library with the tyrosine-phosphorylated C terminus of the epidermal growth factor receptor by Daly et al identified a novel member of the GRB7 gene family, designated GRB14. In addition to a pleckstrin homology domain-containing central region homologous to the Caenorhabditis elegans protein F10E9.6/mig 10 and a C-terminal Src homology 2 (SH2) domain, a conserved N-terminal motif, P(S/A)IPNPFPEL, can be included as a hallmark of this family.
General function
Receptor, Intracellular signaling cascade
Comment
Grb14 is a target for a PDGF-regulated serine kinase, an interaction that does not require PDGFR-Grb14 association. Kasus-Jacobi et al. (1998) identified the rat adapter Grb14 as an inhibitor of insulin actions.
Cellular localization
Cytoplasmic
Comment
Ovarian function
Luteinization
Comment
Grb14 mRNA Levels During Follicular Deviation in Cattle are Higher in Granulosa Cells of Subordinate Compared to Dominant Follicles. Bohrer R et al. The growth factor receptor-bound protein 14 (Grb14) is a cellular adapter protein belonging to the Grb7 family of proteins. Studies with human and rodent cells have demonstrated that Grb14 acts as a negative regulator of tyrosine kinase receptor signalling through the MAPK and PI3K pathways. In cattle, tyrosine kinase receptors are activated during follicular development but the role of Grb14 in this process has not yet been investigated. Therefore, the aim of the present study was to characterize Grb14 mRNA expression in ovarian somatic cells during follicular growth and deviation in cattle. We found Grb14 mRNA expressed in both granulosa and theca cells derived from follicles at different stages of development (3-5?, 6-8, >8?mm in diameter). The abundance of mRNA for Grb14 was higher in granulosa cells of subordinate compared with those from dominant follicles at days 3 and 4 of the follicular wave (p??0.05). These findings suggest that Grb14 may play a regulatory role in granulosa cells during follicular deviation in cattle.////////////////
Growth factor receptor-bound protein 14: a potential new gene associated with oocyte competence. Rosa PR et al. Summary The Grb14 protein is a member of the Grb7 protein family. This protein family acts by binding to tyrosine kinase receptors, promoting cell proliferation and differentiation. There is evidence of the involvement of tyrosine kinase factors in the bovine oocyte maturation process. However, Grb14 has not been studied for bovine cumulus-oocyte complexes (COCs). The aim of the present study was to characterize Grb14 mRNA expression in bovine COCs during follicular development. Furthermore, we demonstrated that the expression of Grb14 mRNA is not regulated by estradiol. mRNA expression of Grb14 was assessed in 480 COCs from follicles of different sizes (1-3, 4-6, 6-8 or >8mm) by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Grb14 mRNA expression decreased in COCs throughout follicular growth (P<0.05). The role of estradiol in the expression of Grb14 mRNA in COCs was studied. Grb14 mRNA abundance did not differ in COCs cultured in the presence or absence of 17-estradiol or fulvestrant. In conclusion, we showed that Grb14 mRNA is downregulated in COCs during antral follicle development, a finding that suggests a role for Grb14 in oocyte competence.
Expression regulated by
LH
Comment
Gene expression decreased. Luteinization of porcine preovulatory follicles leads to systematic changes in follicular gene expression. Agca C et al. The LH surge initiates the luteinization of preovulatory follicles and causes hormonal and structural changes that ultimately lead to ovulation and the formation of corpora lutea. The objective of the study was to examine gene expression in ovarian follicles (n = 11) collected from pigs (Sus scrofa domestica) approaching estrus (estrogenic preovulatory follicle; n = 6 follicles from two sows) and in ovarian follicles collected from pigs on the second day of estrus (preovulatory follicles that were luteinized but had not ovulated; n = 5 follicles from two sows). The follicular status within each follicle was confirmed by follicular fluid analyses of estradiol and progesterone ratios. Microarrays were made from expressed sequence tags that were isolated from cDNA libraries of porcine ovary. Gene expression was measured by hybridization of fluorescently labeled cDNA (preovulatory estrogenic or -luteinized) to the microarray. Microarray analyses detected 107 and 43 genes whose expression was decreased or increased (respectively) during the transition from preovulatory estrogenic to -luteinized (P<0.01). Cells within preovulatory estrogenic follicles had a gene-expression profile of proliferative and metabolically active cells that were responding to oxidative stress. Cells within preovulatory luteinized follicles had a gene-expression profile of nonproliferative and migratory cells with angiogenic properties. Approximately, 40% of the discovered genes had unknown function.
Ovarian localization
Granulosa, Theca
Comment
GRB14 mRNA was expressed at high levels in the liver, kidney, pancreas, testis, ovary, heart, and skeletal muscle. (Daly et al., 1996).