{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSHB is a multifunctional adaptor protein that links activated receptor tyrosine kinases to the regulation of the actin cytoskeleton and cell motility. In studies of growth hormone and platelet‐derived growth factor signaling, SHB (often referred to as SH2‐Bβ) was shown to potentiate cell movement by recruiting Rac and potentially other actin‐regulating proteins. Similarly, SHB is essential in mediating Eph receptor functions, where its phosphotyrosine sites serve as docking sites for cytoskeletal regulators such as Nck, RasGAP, and Rac GAP proteins, thereby orchestrating heterotypic cell segregation and directional movement."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neural and immune contexts, SHB couples receptor signaling to differentiation and survival pathways. It interacts with the RET receptor in response to glial-cell-line-derived neurotrophic factor (GDNF) to facilitate neurite outgrowth in mesencephalic neurons. In T lymphocytes, SHB promotes the assembly of key signaling complexes including SLP-76, Gads, Vav, and ZAP70 at lipid rafts following T cell receptor stimulation, and it further participates in interleukin-2 receptor signaling by binding phosphorylated sites on the IL-2 receptor β and γ chains to modulate apoptotic responses in T and natural killer cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, SHB plays an important role in metabolic regulation and oncogenesis. It operates downstream of several tyrosine kinase receptors to modulate glucose homeostasis and pancreatic β-cell function, notably by enhancing PDX-1 and insulin expression in conjunction with angiogenic factors. In the context of hematopoietic malignancies, elevated SHB expression has been linked to poorer survival in patients with acute myeloid leukemia and is embedded within a network of genes associated with immune, vascular, and apoptotic features. Finally, studies analyzing available antibodies underscore the technical challenges in reliably detecting endogenous SHB, emphasizing the need for carefully validated reagents to further dissect its diverse biological roles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Diakonova, David R Gunter, James Herrington, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SH2-Bbeta is a Rac-binding protein that regulates cell motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111138200"}], "href": "https://doi.org/10.1074/jbc.M111138200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11786545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11786545"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Melany J Wagner, Marilyn S Hsiung, Gerald D Gish, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Shb scaffold binds the Nck adaptor protein, p120 RasGAP, and Chimaerins and thereby facilitates heterotypic cell segregation by the receptor EphB2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.009276"}], "href": "https://doi.org/10.1074/jbc.RA119.009276"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32060095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32060095"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yong Zhang, Wei Zhu, Yong-Gang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of SH2-Bbeta with RET is involved in signaling of GDNF-induced neurite outgrowth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02845"}], "href": "https://doi.org/10.1242/jcs.02845"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16569669"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16569669"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Cecilia K Lindholm, Maria L Henriksson, Bengt Hallberg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Shb links SLP-76 and Vav with the CD3 complex in Jurkat T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Biochem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1432-1033.2002.03008.x"}], "href": "https://doi.org/10.1046/j.1432-1033.2002.03008.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12084069"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12084069"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Cecilia K Lindholm "}, {"type": "b", "children": [{"type": "t", "text": "IL-2 receptor signaling through the Shb adapter protein in T and NK cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)02016-8"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "02016-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12200137"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12200137"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Michael Welsh, Maria Jamalpour, Guangxiang Zang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of the Src Homology-2 domain containing protein B (SHB) in β cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Endocrinol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JME-15-0228"}], "href": "https://doi.org/10.1530/JME-15-0228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26489764"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26489764"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Johan Saldeen, Vitezslav Kriz, Nina Agren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SHB and angiogenic factors promote ES cell differentiation to insulin-producing cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.03.129"}], "href": "https://doi.org/10.1016/j.bbrc.2006.03.129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16630561"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16630561"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Maria Jamalpour, Xiujuan Li, Lucia Cavelier, et al. 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