2022
DOI: 10.1007/s13402-022-00698-1
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A comprehensive review of SHP2 and its role in cancer

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Cited by 64 publications
(64 citation statements)
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“…The type 11 non-receptor tyrosine-protein phosphatase SHP2, encoded by the PTPN11 gene, is a critical regulator of signal transduction. 1 It acts on a variety of downstream receptors and cytoplasmic kinases to regulate cell survival and proliferation primarily through activation of the Ras-Raf-MEK-ERK pathway. 2,3 It also functions as a key modulator of the programmed cell death 1 (PD-1) and B-and T-lymphocyte attenuator (BTLA) immune checkpoint pathways.…”
Section: Introductionmentioning
confidence: 99%
“…The type 11 non-receptor tyrosine-protein phosphatase SHP2, encoded by the PTPN11 gene, is a critical regulator of signal transduction. 1 It acts on a variety of downstream receptors and cytoplasmic kinases to regulate cell survival and proliferation primarily through activation of the Ras-Raf-MEK-ERK pathway. 2,3 It also functions as a key modulator of the programmed cell death 1 (PD-1) and B-and T-lymphocyte attenuator (BTLA) immune checkpoint pathways.…”
Section: Introductionmentioning
confidence: 99%
“…Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2), also called PTPN11, is a nonreceptor-type protein tyrosine phosphatase (PTP). SHP2 is widely expressed in various tissues and controls diverse cellular signaling pathways involved in cell proliferation, growth, differentiation, migration, and morphogenesis (Asmamaw et al, 2022). SHP2 contains two Src homology 2 (SH2) domains, N-SH2 (residues 1−103) and C-SH2 (residues 111−213), followed by a phosphatase domain (residues 224−525) and an unstructured loop region (residues 529−593).…”
Section: Introductionmentioning
confidence: 99%
“…Aberrant regulation of SHP2 activity is closely implicated in RAS-MAPK pathway-associated genetic and developmental diseases, called RASopathies. They include various cancers such as neuroblastoma, lung cancer, colon cancer, juvenile myelomonocytic leukemia, and acute myelogenous leukemia (Huang et al, 2014;Zhang et al, 2015;Asmamaw et al, 2022) and developmental disorders such as Noonan syndrome and LEOPARD syndrome 1 (Tartaglia et al, 2001;Siegfried et al, 2017). Critically, a number of shp2 genetic mutations have been reported in RASopathy patients, most of which interfere with the inhibitory recognition of the phosphatase domain by N-SH2, leading to uncontrolled upregulation of its activity (Siegfried et al, 2017;Dong et al, 2021).…”
Section: Introductionmentioning
confidence: 99%
“…Upon activation, SHP2 can act on several signaling pathways, mainly promoting signaling. Its role in RAS/MAPK, AKT, and JAK/STAT pathways is best established (Tajan et al, 2015b;Asmamaw et al, 2022). SHP2 signaling is cell type-, developmental stage-and stimulus-dependent.…”
mentioning
confidence: 99%
“…It binds to GAB1/GRB2/SOS1 protein complex as a docking protein at the plasma membrane to facilitate activation of RAS (Bennett et al, 1994;Li et al, 1994). Recruitment of GAB proteins established SHP2's role in activation of PI3K signaling (Asmamaw et al, 2022). The direct activation of RAS by dephosphorylation of Tyr 32 on RAS has also been reported (Bunda et al, 2015).…”
mentioning
confidence: 99%