{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GAREM2 is a brain‐enriched adaptor protein that plays a pivotal role in transducing growth factor signals to the Erk/MAPK pathway. Upon stimulation with epidermal growth factor (EGF) or insulin‐like growth factor 1, GAREM2 is tyrosine phosphorylated at specific residues that are essential for binding to Grb2, thereby regulating Erk activity and stimulating neuronal differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Functional studies in knockout mice have further demonstrated that loss of GAREM2 in the brain leads to altered behavioral phenotypes, including reduced anxiety and impaired neurite extension, underscoring its role in maintaining proper neural network formation and higher brain functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, the distinct subcellular distribution of GAREM2—characterized by growth factor-induced aggregation into granules mediated by a unique glycine-rich region that also helps regulate its phosphorylation state—suggests that its compartmentalization may be critical for its signal transduction functions and could have implications in neurodegenerative disease processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomonori Taniguchi, Shigeru Tanaka, Ayumi Ishii, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A brain-specific Grb2-associated regulator of extracellular signal-regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) (GAREM) subtype, GAREM2, contributes to neurite outgrowth of neuroblastoma cells by regulating Erk signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.492520"}], "href": "https://doi.org/10.1074/jbc.M113.492520"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24003223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24003223"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tasuku Nishino, Kota Tamada, Akane Maeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Behavioral analysis in mice deficient for GAREM2 (Grb2-associated regulator of Erk/MAPK subtype2) that is a subtype of highly expressing in the brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Brain (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13041-019-0512-x"}], "href": "https://doi.org/10.1186/s13041-019-0512-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31718706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31718706"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tasuku Nishino, Tsuyoshi Oshika, Moriatsu Kyan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of the glycine-rich domain in GAREM2 on its unique subcellular localization upon EGF stimulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s11658-021-00260-1"}], "href": "https://doi.org/10.1186/s11658-021-00260-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33931009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33931009"}]}]}]}