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New page: '''Unreleased structure''' The entry 5ew8 is ON HOLD Authors: Ogg, D., Breed, J. Description: FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693 [[Category: Unreleased Str...
 
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'''Unreleased structure'''


The entry 5ew8 is ON HOLD
==FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693==
<StructureSection load='5ew8' size='340' side='right'caption='[[5ew8]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ew8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EW8 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.63&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5SF:~{N}-(3,5-DIMETHOXYPHENYL)-~{N}-[3-(1-METHYLPYRAZOL-4-YL)QUINOXALIN-6-YL]-~{N}-PROPAN-2-YL-ETHANE-1,2-DIAMINE'>5SF</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5ew8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ew8 OCA], [https://pdbe.org/5ew8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ew8 RCSB], [https://www.ebi.ac.uk/pdbsum/5ew8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ew8 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN] Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:[https://omim.org/entry/101600 101600]; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.<ref>PMID:20139426</ref> <ref>PMID:7874169</ref>  Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:[https://omim.org/entry/147950 147950]. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).<ref>PMID:20139426</ref> <ref>PMID:12627230</ref> <ref>PMID:15001591</ref> <ref>PMID:15605412</ref> <ref>PMID:15845591</ref> <ref>PMID:16882753</ref> <ref>PMID:16764984</ref> <ref>PMID:16757108</ref> <ref>PMID:16606836</ref> <ref>PMID:17154279</ref>  Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:[https://omim.org/entry/166250 166250]; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.<ref>PMID:20139426</ref> <ref>PMID:15625620</ref> <ref>PMID:16470795</ref>  Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:[https://omim.org/entry/190440 190440]. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.<ref>PMID:20139426</ref> <ref>PMID:11173846</ref>  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.<ref>PMID:20139426</ref>  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity.  Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
== Function ==
[https://www.uniprot.org/uniprot/FGFR1_HUMAN FGFR1_HUMAN] Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.<ref>PMID:20139426</ref> <ref>PMID:1379697</ref> <ref>PMID:1379698</ref> <ref>PMID:8622701</ref> <ref>PMID:8663044</ref> <ref>PMID:11353842</ref> <ref>PMID:12181353</ref> <ref>PMID:15117958</ref> <ref>PMID:16597617</ref> <ref>PMID:17623664</ref> <ref>PMID:17311277</ref> <ref>PMID:18480409</ref> <ref>PMID:19261810</ref> <ref>PMID:19224897</ref> <ref>PMID:21765395</ref> <ref>PMID:10830168</ref> <ref>PMID:19665973</ref> <ref>PMID:20133753</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Frequent genetic alterations discovered in FGFRs and evidence implicating some as drivers in diverse tumors has been accompanied by rapid progress in targeting FGFRs for anticancer treatments. Wider assessment of the impact of genetic changes on the activation state and drug responses is needed to better link the genomic data and treatment options. We here apply a direct comparative and comprehensive analysis of FGFR3 kinase domain variants representing the diversity of point-mutations reported in this domain. We reinforce the importance of N540K and K650E and establish that not all highly activating mutations (for example R669G) occur at high-frequency and conversely, that some "hotspots" may not be linked to activation. Further structural characterization consolidates a mechanistic view of FGFR kinase activation and extends insights into drug binding. Importantly, using several inhibitors of particular clinical interest (AZD4547, BGJ-398, TKI258, JNJ42756493 and AP24534), we find that some activating mutations (including different replacements of the same residue) result in distinct changes in their efficacy. Considering that there is no approved inhibitor for anticancer treatments based on FGFR-targeting, this information will be immediately translatable to ongoing clinical trials.


Authors: Ogg, D., Breed, J.
Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use.,Patani H, Bunney TD, Thiyagarajan N, Norman RA, Ogg D, Breed J, Ashford P, Potterton A, Edwards M, Williams SV, Thomson GS, Pang CS, Knowles MA, Breeze AL, Orengo C, Phillips C, Katan M Oncotarget. 2016 Mar 16. doi: 10.18632/oncotarget.8132. PMID:26992226<ref>PMID:26992226</ref>


Description: FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Ogg, D]]
<div class="pdbe-citations 5ew8" style="background-color:#fffaf0;"></div>
[[Category: Breed, J]]
 
==See Also==
*[[Fibroblast growth factor receptor 3D receptor|Fibroblast growth factor receptor 3D receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Breed J]]
[[Category: Ogg D]]

Latest revision as of 11:28, 12 July 2023

FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693FIBROBLAST GROWTH FACTOR RECEPTOR 1 IN COMPLEX WITH JNJ-4275693

Structural highlights

5ew8 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.63Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FGFR1_HUMAN Defects in FGFR1 are a cause of Pfeiffer syndrome (PS) [MIM:101600; also known as acrocephalosyndactyly type V (ACS5). PS is characterized by craniosynostosis (premature fusion of the skull sutures) with deviation and enlargement of the thumbs and great toes, brachymesophalangy, with phalangeal ankylosis and a varying degree of soft tissue syndactyly.[1] [2] Defects in FGFR1 are the cause of hypogonadotropic hypogonadism 2 with or without anosmia (HH2) [MIM:147950. A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. In some cases, it is associated with non-reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH).[3] [4] [5] [6] [7] [8] [9] [10] [11] [12] Defects in FGFR1 are the cause of osteoglophonic dysplasia (OGD) [MIM:166250; also known as osteoglophonic dwarfism. OGD is characterized by craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as by rhizomelic dwarfism and nonossifying bone lesions. Inheritance is autosomal dominant.[13] [14] [15] Defects in FGFR1 are the cause of trigonocephaly type 1 (TRIGNO1) [MIM:190440. A keel-shaped deformation of the forehead resulting from premature fusion of the frontal suture. Trigonocephaly may occur also as a part of a syndrome.[16] [17] Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell leukemia lymphoma syndrome (SCLL). Translocation t(8;13)(p11;q12) with ZMYM2. SCLL usually presents as lymphoblastic lymphoma in association with a myeloproliferative disorder, often accompanied by pronounced peripheral eosinophilia and/or prominent eosinophilic infiltrates in the affected bone marrow.[18] Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(6;8)(q27;p11) with FGFR1OP. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, FGFR1OP-FGFR1 or FGFR1-FGFR1OP may exhibit constitutive kinase activity and be responsible for the transforming activity. Note=A chromosomal aberration involving FGFR1 may be a cause of stem cell myeloproliferative disorder (MPD). Translocation t(8;9)(p12;q33) with CEP110. MPD is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion protein CEP110-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.

Function

FGFR1_HUMAN Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.[19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] [36]

Publication Abstract from PubMed

Frequent genetic alterations discovered in FGFRs and evidence implicating some as drivers in diverse tumors has been accompanied by rapid progress in targeting FGFRs for anticancer treatments. Wider assessment of the impact of genetic changes on the activation state and drug responses is needed to better link the genomic data and treatment options. We here apply a direct comparative and comprehensive analysis of FGFR3 kinase domain variants representing the diversity of point-mutations reported in this domain. We reinforce the importance of N540K and K650E and establish that not all highly activating mutations (for example R669G) occur at high-frequency and conversely, that some "hotspots" may not be linked to activation. Further structural characterization consolidates a mechanistic view of FGFR kinase activation and extends insights into drug binding. Importantly, using several inhibitors of particular clinical interest (AZD4547, BGJ-398, TKI258, JNJ42756493 and AP24534), we find that some activating mutations (including different replacements of the same residue) result in distinct changes in their efficacy. Considering that there is no approved inhibitor for anticancer treatments based on FGFR-targeting, this information will be immediately translatable to ongoing clinical trials.

Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use.,Patani H, Bunney TD, Thiyagarajan N, Norman RA, Ogg D, Breed J, Ashford P, Potterton A, Edwards M, Williams SV, Thomson GS, Pang CS, Knowles MA, Breeze AL, Orengo C, Phillips C, Katan M Oncotarget. 2016 Mar 16. doi: 10.18632/oncotarget.8132. PMID:26992226[37]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  2. ↑ Muenke M, Schell U, Hehr A, Robin NH, Losken HW, Schinzel A, Pulleyn LJ, Rutland P, Reardon W, Malcolm S, et al.. A common mutation in the fibroblast growth factor receptor 1 gene in Pfeiffer syndrome. Nat Genet. 1994 Nov;8(3):269-74. PMID:7874169 doi:http://dx.doi.org/10.1038/ng1194-269
  3. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  4. ↑ Dode C, Levilliers J, Dupont JM, De Paepe A, Le Du N, Soussi-Yanicostas N, Coimbra RS, Delmaghani S, Compain-Nouaille S, Baverel F, Pecheux C, Le Tessier D, Cruaud C, Delpech M, Speleman F, Vermeulen S, Amalfitano A, Bachelot Y, Bouchard P, Cabrol S, Carel JC, Delemarre-van de Waal H, Goulet-Salmon B, Kottler ML, Richard O, Sanchez-Franco F, Saura R, Young J, Petit C, Hardelin JP. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. Epub 2003 Mar 10. PMID:12627230 doi:10.1038/ng1122
  5. ↑ Sato N, Katsumata N, Kagami M, Hasegawa T, Hori N, Kawakita S, Minowada S, Shimotsuka A, Shishiba Y, Yokozawa M, Yasuda T, Nagasaki K, Hasegawa D, Hasegawa Y, Tachibana K, Naiki Y, Horikawa R, Tanaka T, Ogata T. Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients. J Clin Endocrinol Metab. 2004 Mar;89(3):1079-88. PMID:15001591
  6. ↑ Albuisson J, Pecheux C, Carel JC, Lacombe D, Leheup B, Lapuzina P, Bouchard P, Legius E, Matthijs G, Wasniewska M, Delpech M, Young J, Hardelin JP, Dode C. Kallmann syndrome: 14 novel mutations in KAL1 and FGFR1 (KAL2). Hum Mutat. 2005 Jan;25(1):98-9. PMID:15605412 doi:10.1002/humu.9298
  7. ↑ Sato N, Hasegawa T, Hori N, Fukami M, Yoshimura Y, Ogata T. Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of the gene for fibroblast growth factor receptor 1: report of three families: case report. Hum Reprod. 2005 Aug;20(8):2173-8. Epub 2005 Apr 21. PMID:15845591 doi:dei052
  8. ↑ Trarbach EB, Costa EM, Versiani B, de Castro M, Baptista MT, Garmes HM, de Mendonca BB, Latronico AC. Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia. J Clin Endocrinol Metab. 2006 Oct;91(10):4006-12. Epub 2006 Aug 1. PMID:16882753 doi:10.1210/jc.2005-2793
  9. ↑ Pitteloud N, Meysing A, Quinton R, Acierno JS Jr, Dwyer AA, Plummer L, Fliers E, Boepple P, Hayes F, Seminara S, Hughes VA, Ma J, Bouloux P, Mohammadi M, Crowley WF Jr. Mutations in fibroblast growth factor receptor 1 cause Kallmann syndrome with a wide spectrum of reproductive phenotypes. Mol Cell Endocrinol. 2006 Jul 25;254-255:60-9. Epub 2006 Jun 9. PMID:16764984 doi:S0303-7207(06)00223-1
  10. ↑ Zenaty D, Bretones P, Lambe C, Guemas I, David M, Leger J, de Roux N. Paediatric phenotype of Kallmann syndrome due to mutations of fibroblast growth factor receptor 1 (FGFR1). Mol Cell Endocrinol. 2006 Jul 25;254-255:78-83. Epub 2006 Jun 6. PMID:16757108 doi:10.1016/j.mce.2006.04.006
  11. ↑ Pitteloud N, Acierno JS Jr, Meysing A, Eliseenkova AV, Ma J, Ibrahimi OA, Metzger DL, Hayes FJ, Dwyer AA, Hughes VA, Yialamas M, Hall JE, Grant E, Mohammadi M, Crowley WF Jr. Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6281-6. Epub 2006 Apr 10. PMID:16606836 doi:0600962103
  12. ↑ Dode C, Fouveaut C, Mortier G, Janssens S, Bertherat J, Mahoudeau J, Kottler ML, Chabrolle C, Gancel A, Francois I, Devriendt K, Wolczynski S, Pugeat M, Pineiro-Garcia A, Murat A, Bouchard P, Young J, Delpech M, Hardelin JP. Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. Hum Mutat. 2007 Jan;28(1):97-8. PMID:17154279 doi:10.1002/humu.9470
  13. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  14. ↑ White KE, Cabral JM, Davis SI, Fishburn T, Evans WE, Ichikawa S, Fields J, Yu X, Shaw NJ, McLellan NJ, McKeown C, Fitzpatrick D, Yu K, Ornitz DM, Econs MJ. Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. Am J Hum Genet. 2005 Feb;76(2):361-7. Epub 2004 Dec 28. PMID:15625620 doi:S0002-9297(07)62588-9
  15. ↑ Farrow EG, Davis SI, Mooney SD, Beighton P, Mascarenhas L, Gutierrez YR, Pitukcheewanont P, White KE. Extended mutational analyses of FGFR1 in osteoglophonic dysplasia. Am J Med Genet A. 2006 Mar 1;140(5):537-9. PMID:16470795 doi:10.1002/ajmg.a.31106
  16. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  17. ↑ Kress W, Petersen B, Collmann H, Grimm T. An unusual FGFR1 mutation (fibroblast growth factor receptor 1 mutation) in a girl with non-syndromic trigonocephaly. Cytogenet Cell Genet. 2000;91(1-4):138-40. PMID:11173846
  18. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  19. ↑ Miura K, Miura S, Yoshiura K, Seminara S, Hamaguchi D, Niikawa N, Masuzaki H. A case of Kallmann syndrome carrying a missense mutation in alternatively spliced exon 8A encoding the immunoglobulin-like domain IIIb of fibroblast growth factor receptor 1. Hum Reprod. 2010 Apr;25(4):1076-80. doi: 10.1093/humrep/deq006. Epub 2010 Feb 6. PMID:20139426 doi:10.1093/humrep/deq006
  20. ↑ Peters KG, Marie J, Wilson E, Ives HE, Escobedo J, Del Rosario M, Mirda D, Williams LT. Point mutation of an FGF receptor abolishes phosphatidylinositol turnover and Ca2+ flux but not mitogenesis. Nature. 1992 Aug 20;358(6388):678-81. PMID:1379697 doi:http://dx.doi.org/10.1038/358678a0
  21. ↑ Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honegger AM, Jaye M, Schlessinger J. Point mutation in FGF receptor eliminates phosphatidylinositol hydrolysis without affecting mitogenesis. Nature. 1992 Aug 20;358(6388):681-4. PMID:1379698 doi:http://dx.doi.org/10.1038/358681a0
  22. ↑ Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger J. Identification of six novel autophosphorylation sites on fibroblast growth factor receptor 1 and elucidation of their importance in receptor activation and signal transduction. Mol Cell Biol. 1996 Mar;16(3):977-89. PMID:8622701
  23. ↑ Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M. Receptor specificity of the fibroblast growth factor family. J Biol Chem. 1996 Jun 21;271(25):15292-7. PMID:8663044
  24. ↑ Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I. Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6074-9. Epub 2001 May 15. PMID:11353842 doi:10.1073/pnas.111114298
  25. ↑ Cross MJ, Lu L, Magnusson P, Nyqvist D, Holmqvist K, Welsh M, Claesson-Welsh L. The Shb adaptor protein binds to tyrosine 766 in the FGFR-1 and regulates the Ras/MEK/MAPK pathway via FRS2 phosphorylation in endothelial cells. Mol Biol Cell. 2002 Aug;13(8):2881-93. PMID:12181353 doi:10.1091/mbc.E02-02-0103
  26. ↑ Hu Y, Fang X, Dunham SM, Prada C, Stachowiak EK, Stachowiak MK. 90-kDa ribosomal S6 kinase is a direct target for the nuclear fibroblast growth factor receptor 1 (FGFR1): role in FGFR1 signaling. J Biol Chem. 2004 Jul 9;279(28):29325-35. Epub 2004 Apr 26. PMID:15117958 doi:10.1074/jbc.M311144200
  27. ↑ Zhang X, Ibrahimi OA, Olsen SK, Umemori H, Mohammadi M, Ornitz DM. Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. J Biol Chem. 2006 Jun 9;281(23):15694-700. Epub 2006 Apr 4. PMID:16597617 doi:10.1074/jbc.M601252200
  28. ↑ Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-95. Epub 2007 Jul 10. PMID:17623664 doi:10.1074/jbc.M704165200
  29. ↑ Citores L, Bai L, Sorensen V, Olsnes S. Fibroblast growth factor receptor-induced phosphorylation of STAT1 at the Golgi apparatus without translocation to the nucleus. J Cell Physiol. 2007 Jul;212(1):148-56. PMID:17311277 doi:10.1002/jcp.21014
  30. ↑ Haugsten EM, Malecki J, Bjorklund SM, Olsnes S, Wesche J. Ubiquitination of fibroblast growth factor receptor 1 is required for its intracellular sorting but not for its endocytosis. Mol Biol Cell. 2008 Aug;19(8):3390-403. doi: 10.1091/mbc.E07-12-1219. Epub 2008, May 14. PMID:18480409 doi:10.1091/mbc.E07-12-1219
  31. ↑ Dunham-Ems SM, Lee YW, Stachowiak EK, Pudavar H, Claus P, Prasad PN, Stachowiak MK. Fibroblast growth factor receptor-1 (FGFR1) nuclear dynamics reveal a novel mechanism in transcription control. Mol Biol Cell. 2009 May;20(9):2401-12. doi: 10.1091/mbc.E08-06-0600. Epub 2009, Mar 4. PMID:19261810 doi:10.1091/mbc.E08-06-0600
  32. ↑ Lew ED, Furdui CM, Anderson KS, Schlessinger J. The precise sequence of FGF receptor autophosphorylation is kinetically driven and is disrupted by oncogenic mutations. Sci Signal. 2009 Feb 17;2(58):ra6. doi: 10.1126/scisignal.2000021. PMID:19224897 doi:10.1126/scisignal.2000021
  33. ↑ Persaud A, Alberts P, Hayes M, Guettler S, Clarke I, Sicheri F, Dirks P, Ciruna B, Rotin D. Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. EMBO J. 2011 Jul 15;30(16):3259-73. doi: 10.1038/emboj.2011.234. PMID:21765395 doi:10.1038/emboj.2011.234
  34. ↑ Plotnikov AN, Hubbard SR, Schlessinger J, Mohammadi M. Crystal structures of two FGF-FGFR complexes reveal the determinants of ligand-receptor specificity. Cell. 2000 May 12;101(4):413-24. PMID:10830168
  35. ↑ Bae JH, Lew ED, Yuzawa S, Tome F, Lax I, Schlessinger J. The selectivity of receptor tyrosine kinase signaling is controlled by a secondary SH2 domain binding site. Cell. 2009 Aug 7;138(3):514-24. PMID:19665973 doi:S0092-8674(09)00631-X
  36. ↑ Bae JH, Boggon TJ, Tome F, Mandiyan V, Lax I, Schlessinger J. Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2866-71. Epub 2010 Jan 26. PMID:20133753
  37. ↑ Patani H, Bunney TD, Thiyagarajan N, Norman RA, Ogg D, Breed J, Ashford P, Potterton A, Edwards M, Williams SV, Thomson GS, Pang CS, Knowles MA, Breeze AL, Orengo C, Phillips C, Katan M. Landscape of activating cancer mutations in FGFR kinases and their differential responses to inhibitors in clinical use. Oncotarget. 2016 Mar 16. doi: 10.18632/oncotarget.8132. PMID:26992226 doi:http://dx.doi.org/10.18632/oncotarget.8132

5ew8, resolution 1.63Å

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