We identified 17 nominally associated genes among females (Excel Table S5), four of which yielded FDR-significant associations: GRB10
, ILK, CPA4, and thrombospondin type 1 domain containing 7A (THSD7A).
Poulogiannis et al., "Phosphoproteomic analysis identifies Grb10
as an mTORC1 substrate that negatively regulates insulin signaling," Science, vol.
protein is known to have different isoforms that are responsible for binding several trans-membrane tyrosine-kinase receptors, including the insulin receptor (IR), the insulin-like growth factor receptor (IGF-IR) and the epidermal growth factor receptor (EGFR) (HOLT & SIDDLE, 2005).
is stimulated by cold stress, which causes the body to burn energy.
The team, led by researchers from the School of Medicine at The University of Texas Health Science Center at San Antonio, also found that a protein, Grb10
, serves as the on-off switch for mTORC1 signaling and the "beigeing" of fat.
Growth factor receptor-bound protein 10 (GRB10
) is a recently discovered substrate of mTOR that is activated by mTOR phosphorylation and negatively controls insulin-PI3K-AKT signaling pathway by inhibiting the insulin receptor in its active form .
Ward, "Disruption of the imprinted Grb10
gene leads to disproportionate overgrowth by an Igf2-independent mechanism," Proceedings of the National Academy of Sciences of the United States of America, vol.
None of the identified DMCs at the other top imprinted genes--growth factor receptor bound protein 10 (Grb10
), pleiomorphic adenoma gene-like 1 (Plagll), phosphodiesterase 10A (Pde10a), Klf14, and small nuclear ribonucleoprotein polypeptide N (Snrpn)--fell in known murine ICRs.
miR-504 may enhance extracellular regulated protein kinase 1/2 (ERK1/2) activation by targeting Grb10
and thereby contribute to changes in the VSMC phenotype.
Ryan et al., "Dual ablation of Grb10
and Grb14 in mice reveals their combined role in regulation of insulin signaling and glucose homeostasis," Molecular Endocrinology, vol.
By blocking the function of Grb10
- nicknamed the 'Hulk' protein - while mice were in the womb, they were considerably stronger and more muscular at birth than normal mice, the researchers said.
Among these, 15 genes were maternally expressed and 18 genes were paternally expressed, and one gene (GRB10
) had isoform-dependent expression.