PTPN11
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| Location (UCSC) | Chr 12: 112.42 – 112.51 Mb | Chr 5: 121.27 – 121.33 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.[5][6]
PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia.[7]
Structure and function
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This phosphatase, along with its paralogue,
Upon binding to target phospho-tyrosyl residues, the N-terminal SH2 domain is released from the PTP domain, catalytically activating the enzyme by relieving this auto-inhibition.
Genetic diseases associated with PTPN11
Missense mutations in the PTPN11 locus are associated with both
It has also been associated with metachondromatosis.[9]
Noonan syndrome
In the case of Noonan syndrome, mutations are broadly distributed throughout the coding region of the gene but all appear to result in hyper-activated, or unregulated mutant forms of the protein. Most of these mutations disrupt the binding interface between the N-SH2 domain and catalytic core necessary for the enzyme to maintain its auto-inhibited conformation.[10]
Leopard syndrome
The mutations that cause Leopard syndrome are restricted regions affecting the catalytic core of the enzyme producing catalytically impaired Shp2 variants.[11] It is currently unclear how mutations that give rise to mutant variants of Shp2 with biochemically opposite characteristics result in similar human genetic syndromes.
Cancer associated with PTPN11
Patients with a subset of Noonan syndrome PTPN11 mutations also have a higher prevalence of
Interactions
PTPN11 has been shown to
- CagA,[15]
- Cbl gene,[16]
- CD31,[19][20][21][22]
- CEACAM1,[23]
- Epidermal growth factor receptor,[24][25]
- Erk[26][27]
- FRS2,[28][29][30]
- GAB2,[33][34][35][36]
- GAB3,[37]
- Glycoprotein 130,[38][39][40]
- Growth hormone receptor,[49][50]
- HoxA10,[51]
- Insulin receptor,[52][53]
- Insulin-like growth factor 1 receptor,[54][55]
- Janus kinase 1,[38][41]
- Janus kinase 2,[41][58][59]
- LAIR1,[60][61]
- LRP1,[62]
- PDGFRB,[63][64]
- Akt[26]
- PLCG2,[33]
- PTK2B,[65]
- SLAMF1,[66][67]
- SOCS3,[38]
- SOS1,[30][68]
- STAT3,[14]
- STAT5A,[69][70] and
- STAT5B.[69]
H Pylori CagA virulence factor
CagA is a protein and
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000179295 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000043733 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 1582162.
- PMID 1280823.
- ^ "Entrez Gene: PTPN11 protein tyrosine phosphatase, non-receptor type 11 (Noonan syndrome 1)".
- PMID 31819097.
- PMID 20577567.
- S2CID 10222262.
- PMID 16377799.
- PMID 15604238.
- PMID 29724895.
- ^ PMID 21575863.
- ^ S2CID 5721063.
- PMID 18519587.
- PMID 7523381.
- PMID 9528781.
- PMID 10801826.
- S2CID 31471121.
- PMID 9774457.
- PMID 9054388.
- PMID 9867848.
- PMID 16729043.
- PMID 7673163.
- ^ ISBN 978-3-540-20560-9.
- ^ PMID 12826400.
- PMID 10650943.
- S2CID 25346661.
- ^ PMID 9632781.
- PMID 11940581.
- PMID 9658397.
- ^ PMID 12135708.
- PMID 11782427.
- PMID 10391903.
- S2CID 24499468.
- PMID 11739737.
and associates transiently with the SH2 domain-containing proteins p85 and SHP2
- ^ PMID 12403768.
- PMID 10946280.
- PMID 9388212.
- ^ PMID 8995399.
- PMID 10747947.
- PMID 8041791.
- PMID 9824671.
- PMID 9362449.
- PMID 10212213.
- S2CID 38211235.
- PMID 8702859.
- PMID 10976913.
- PMID 9632636.
- PMID 19022774.
- PMID 8135823.
- PMID 7493946.
- PMID 10082579.
- PMID 7642582.
- PMID 8505282.
- PMID 9756938.
- PMID 8639815.
- PMID 8912646.
- PMID 10903717.
- PMID 9285412.
- PMID 18381291.
- PMID 11266449.
- PMID 7691811.
- PMID 10880513.
- PMID 11806999.
- PMID 11689425.
- PMID 9344843.
- ^ PMID 10617656.
- PMID 12060651.
- S2CID 1218835.
Further reading
- Marron MB, Hughes DP, McCarthy MJ, Beaumont ER, Brindle NP (2000). "Tie-1 Receptor Tyrosine Kinase Endodomain Interaction with SHP2: Potential Signalling Mechanisms and Roles in Angiogenesis". Angiogenesis. Advances in Experimental Medicine and Biology. Vol. 476. pp. 35–46. PMID 10949653.
- Carter-Su C, Rui L, Stofega MR (2000). "SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone". Recent Prog. Horm. Res. 55: 293–311. PMID 11036942.
- Ion A, Tartaglia M, Song X, Kalidas K, van der Burgt I, Shaw AC, Ming JE, Zampino G, Zackai EH, Dean JC, Somer M, Parenti G, Crosby AH, Patton MA, Gelb BD, Jeffery S (2002). "Absence of PTPN11 mutations in 28 cases of cardiofaciocutaneous (CFC) syndrome". Hum. Genet. 111 (4–5): 421–7. S2CID 27085702.
- Hugues L, Cavé H, Philippe N, Pereira S, Fenaux P, Preudhomme C (2006). "Mutations of PTPN11 are rare in adult myeloid malignancies". Haematologica. 90 (6): 853–4. PMID 15951301.
- Tartaglia M, Gelb BD (2005). "Germ-line and somatic PTPN11 mutations in human disease". European Journal of Medical Genetics. 48 (2): 81–96. PMID 16053901.
- Ogata T, Yoshida R (2006). "PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes". Pediatric Endocrinology Reviews. 2 (4): 669–74. PMID 16208280.
- Feng GS (2007). "Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal and differentiation". Cell Res. 17 (1): 37–41. PMID 17211446.
- Edouard T, Montagner A, Dance M, Conte F, Yart A, Parfait B, Tauber M, Salles JP, Raynal P (2007). "How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?". Cell. Mol. Life Sci. 64 (13): 1585–90. S2CID 25934330.
External links
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