{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ELMO2, a member of the engulfment and cell motility protein family, functions as a multifunctional adaptor that links activated cell surface receptors to the intracellular machinery controlling actin dynamics and microtubule stability. In several cell types, ELMO2 forms complexes with Dock family guanine nucleotide exchange factors, RhoG, and integrin‐linked kinase (ILK) to facilitate Rac1 activation. This cascade drives processes such as lamellipodia formation, front–rear cell polarization, and efficient directional migration and phagocytosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In breast cancer cells, for example, ELMO2 becomes tyrosine‐phosphorylated downstream of receptors such as Axl and EphA2, thereby linking receptor activation to Rac1‐mediated cytoskeletal reorganization that promotes cell migration, invasion, and proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In epidermal keratinocytes, ILK–ELMO2 complexes not only support β1 integrin–dependent directional migration but also contribute, through a Rac1‐dependent mechanism, to the stabilization of microtubule networks in an integrin‐independent manner. This activity is essential for the establishment of adherens junctions and maintenance of tissue integrity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural analyses have revealed that ELMO2 directly engages conserved motifs within the cytoplasmic tails of adhesion G protein–coupled receptors—for example, those of the BAI family—further emphasizing its role as a versatile signaling bridge between membrane receptors and intracellular actin regulators."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, loss‐of‐function mutations or altered expression of ELMO2 have been linked to defects in Rac1‐dependent cell migration, vascular malformations, and even associations with metabolic diseases. These findings underscore the broad physiological impact of ELMO2 in processes ranging from cancer cell invasiveness and tissue repair to developmental homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nao Hiramoto-Yamaki, Shingo Takeuchi, Shuhei Ueda, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Axl phosphorylates Elmo scaffold proteins to promote Rac activation and cell invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00764-14"}], "href": "https://doi.org/10.1128/MCB.00764-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25332238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25332238"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jennifer L Peotter, Jenny Phillips, Tiegang Tong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2016.08.009"}], "href": "https://doi.org/10.1016/j.yexcr.2016.08.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27539661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27539661"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ernest Ho, Lina Dagnino "}, {"type": "b", "children": [{"type": "t", "text": "Epidermal growth factor induction of front-rear polarity and migration in keratinocytes is mediated by integrin-linked kinase and ELMO2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-07-0596"}], "href": "https://doi.org/10.1091/mbc.E11-07-0596"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22160594"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22160594"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ernest Ho, Tames Irvine, Gregory J A Vilk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Integrin-linked kinase interactions with ELMO2 modulate cell polarity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e09-01-0050"}], "href": "https://doi.org/10.1091/mbc.e09-01-0050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19439446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19439446"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bradley C Jackson, Iordanka A Ivanova, Lina Dagnino "}, {"type": "b", "children": [{"type": "t", "text": "An ELMO2-RhoG-ILK network modulates microtubule dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E14-10-1444"}], "href": "https://doi.org/10.1091/mbc.E14-10-1444"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25995380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25995380"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Zhuangfeng Weng, Chenghao Situ, Lin Lin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-07938-9"}], "href": "https://doi.org/10.1038/s41467-018-07938-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30604775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30604775"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Arda Cetinkaya, Jingwei Rachel Xiong, İbrahim Vargel, et al. 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