FRS2

FRS2
사용 가능한 구조
PDB	Ortholog 검색: PDBe RCSB
PDB ID 코드 목록
	1XR0, 2MFQ
식별자
에일리어스	FRS2, FRS2A, FRS2alpha, SNT, SNT-1, SNT1, FRS1A, 섬유아세포 성장인자 수용체 기판 2
외부 ID	OMIM: 607743 MGI: 1100860 HomoloGene: 4846 GeneCard: FRS2
유전자 위치(인간)
크르.	12번 염색체(인간)
끝.	69,579,793 bp
RNA발현패턴
	상단 표시 위치:
	아킬레스건; ; 내피 세포; ; 신경절 융기; ; 랑게르한스 섬; ; 자궁내막간질세포; ; 부고환 말뭉치; ; 담낭; ; 내장글로부페리더스; ; 뇌량; ; 단구;
	추가 참조 표현식 데이터
	추가 참조 표현식 데이터
유전자 존재론
분자 함수	막관통수용체단백질티로신인산화효소어댑터활성; 섬유아세포증식인자수용체결합; 뉴로트로핀TRKA수용체결합; GO:0001948 단백질 결합; 포스파타아제활성화제; 1-아미타디딜이노시톨-3-아미타디올활성; 포스파티딜이노시톨-4,5-이인산3-인산활성;
셀룰러 컴포넌트	세포질; 내염색체; 막; 혈장막; 혈장막의 적분 성분; 내막계; 세포-세포 접합; 세포;
생물학적 과정	아포토시스 과정 조절; G단백질결합수용체신호경로; 심실중격발달; 장기 유도; 막간수용체단백질티로신인산화효소신호전달경로; 제2의 구강을 형성하는 위경련; MAPK 캐스케이드; 카메라형 안구 형성에 관여하는 렌즈 플래코드 형성; 섬유아세포증식인자수용체신호경로; 막간수용체단백질티로신포스파타아제신호전달경로; 카메라형 눈의 렌즈 현상; 전립선 침상 형태 형성에 관여하는 전립선 상피 척수 수목화; ERK1 및 ERK2 캐스케이드 조절; 신경아세포증식; 전뇌 발달; 상피세포증식조절; 전/후축 사양, 배아; 렌즈섬유세포발달; 포스파티딜이노시톨인산생합성법; 포스파티딜이노시톨-3-인산생합성법; 축삭 유도; 심근 세포 분화의 음성 조절; 단백질인산화효소B신호전달양성조절; 신경트로핀TRK수용체신호경로;
	출처:아미고 / QuickGO
맞춤법
	10818
	327826
	ENSG00000166225
	ENSMUSG000020170
	Q8WU20
	Q8C180
NM_006654; NM_001042555; NM_001278351; NM_001278353; NM_001278354;
	NM_001278355; NM_001278356; NM_001278357
	NM_177798
NP_001036020; NP_001265280; NP_001265282; NP_001265283; NP_001265284;
	NP_001265285; NP_001265286; NP_006645
	NP_808466
	위키데이터
인간 보기/편집	마우스 표시/편집

섬유아세포증식인자수용체기판 2는 FRS2유전자에 ^[4]^[5]^[6]^[7]의해 인체 내에서 부호화되는 단백질이다.

FRS2는 특정 활성 수용체 Tyrosine Kinase(RTK)를 여러 다운스트림 신호 경로, 특히 MAPK/ERK, PI3K/AKT /MTOR ^[8]및 PLCδ 경로에 연결하는 80kDa 막 고정 신호 변환 어댑터 단백질(STAP)이다.그것은 전립선암을 ^[9]^[10]포함한 여러 종류의 암에서 과도하게 발현되고 증폭된다.

상호 작용

FRS2는 다음과 상호작용하는 것으로 나타났습니다.

CBL^[11]
FGFR1^[6]^[12]^[13]^[14]
GRB2^[11]^[15]^[16]^[17]
PRKCI^[18]
PTPN11^[19]^[20]^[21]
SOS1^[11]^[17]^[22]
TrkA^[16]
알크^[23]

레퍼런스

^ ^a ^b ^c GRCh38: 앙상블 릴리즈 89: ENSG00000166225 - 앙상블, 2017년 5월
^ "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.
^ Rabin SJ, Cleghon V, Kaplan DR (April 1993). "SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells". Molecular and Cellular Biology. 13 (4): 2203–13. doi:10.1128/mcb.13.4.2203. PMC 359541. PMID 7681142.
^ Wang JK, Xu H, Li HC, Goldfarb M (October 1996). "Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras". Oncogene. 13 (4): 721–9. PMID 8761293.
^ ^a ^b Xu H, Lee KW, Goldfarb M (August 1998). "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins". J Biol Chem. 273 (29): 17987–90. doi:10.1074/jbc.273.29.17987. PMID 9660748.
^ "Entrez Gene: FRS2 Fibroblast growth factor receptor substrate 2".
^ Pawson T, Scott JD (December 1997). "Signaling through scaffold, anchoring, and adaptor proteins". Science. 278 (5346): 2075–80. Bibcode:1997Sci...278.2075P. doi:10.1126/science.278.5346.2075. PMID 9405336.
^ Valencia T, Joseph A, Kachroo N, Darby S, Meakin S, Gnanapragasam VJ (Nov 11, 2011). "Role and expression of FRS2 and FRS3 in prostate cancer". BMC Cancer. 11: 484. doi:10.1186/1471-2407-11-484. PMC 3231952. PMID 22078327.
^ Chen Y, McGee J, Chen X, Doman TN, Gong X, Zhang Y, Hamm N, Ma X, Higgs RE, Bhagwat SV, Buchanan S, Peng SB, Staschke KA, Yadav V, Yue Y, Kouros-Mehr H (2014). "Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets". PLOS ONE. 9 (5): e98293. Bibcode:2014PLoSO...998293C. doi:10.1371/journal.pone.0098293. PMC 4038530. PMID 24874471.
^ ^a ^b ^c Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A (May 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6684–9. Bibcode:2002PNAS...99.6684W. doi:10.1073/pnas.052138899. PMC 124463. PMID 11997436.
^ Yan KS, Kuti M, Yan S, Mujtaba S, Farooq A, Goldfarb MP, Zhou MM (May 2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. 277 (19): 17088–94. doi:10.1074/jbc.M107963200. PMID 11877385.
^ Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I (February 2000). "FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors". Mol. Cell. Biol. 20 (3): 979–89. doi:10.1128/mcb.20.3.979-989.2000. PMC 85215. PMID 10629055.
^ Dhalluin C, Yan KS, Plotnikova O, Lee KW, Zeng L, Kuti M, Mujtaba S, Goldfarb MP, Zhou MM (October 2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell. 6 (4): 921–9. doi:10.1016/S1097-2765(05)00087-0. PMC 5155437. PMID 11090629.
^ Ong SH, Goh KC, Lim YP, Low BC, Klint P, Claesson-Welsh L, Cao X, Tan YH, Guy GR (August 1996). "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochem. Biophys. Res. Commun. 225 (3): 1021–6. doi:10.1006/bbrc.1996.1288. PMID 8780727.
^ ^a ^b Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM (April 1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. 274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. PMID 10092678.
^ ^a ^b Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J (May 1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell. 89 (5): 693–702. doi:10.1016/s0092-8674(00)80252-4. PMID 9182757. S2CID 2187363.
^ Lim YP, Low BC, Lim J, Wong ES, Guy GR (July 1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". J. Biol. Chem. 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. PMID 10383403.
^ Delahaye L, Rocchi S, Van Obberghen E (February 2000). "Potential involvement of FRS2 in insulin signaling". Endocrinology. 141 (2): 621–8. doi:10.1210/endo.141.2.7298. PMID 10650943.
^ Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M (April 2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.
^ Hadari YR, Kouhara H, Lax I, Schlessinger J (July 1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. 18 (7): 3966–73. doi:10.1128/mcb.18.7.3966. PMC 108981. PMID 9632781.
^ Foehr ED, Tatavos A, Tanabe E, Raffioni S, Goetz S, Dimarco E, De Luca M, Bradshaw RA (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB J. 14 (7): 973–81. doi:10.1096/fasebj.14.7.973. PMID 10783152. S2CID 43317719.
^ Degoutin J, Vigny M, Gouzi JY (February 2007). "ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation". FEBS Letters. 581 (4): 727–34. doi:10.1016/j.febslet.2007.01.039. PMID 17274988. S2CID 40978851.

추가 정보

Ong SH, Goh KC, Lim YP, Low BC, Klint P, Claesson-Welsh L, Cao X, Tan YH, Guy GR (1996). "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochem. Biophys. Res. Commun. 225 (3): 1021–6. doi:10.1006/bbrc.1996.1288. PMID 8780727.
Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J (1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell. 89 (5): 693–702. doi:10.1016/S0092-8674(00)80252-4. PMID 9182757. S2CID 2187363.
Hadari YR, Kouhara H, Lax I, Schlessinger J (1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. 18 (7): 3966–73. doi:10.1128/mcb.18.7.3966. PMC 108981. PMID 9632781.
Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM (1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. 274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. PMID 10092678.
Lim YP, Low BC, Lim J, Wong ES, Guy GR (1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". J. Biol. Chem. 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. PMID 10383403.
Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I (2000). "FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors". Mol. Cell. Biol. 20 (3): 979–89. doi:10.1128/MCB.20.3.979-989.2000. PMC 85215. PMID 10629055.
Delahaye L, Rocchi S, Van Obberghen E (2000). "Potential involvement of FRS2 in insulin signaling". Endocrinology. 141 (2): 621–8. doi:10.1210/endo.141.2.7298. PMID 10650943.
Foehr ED, Tatavos A, Tanabe E, Raffioni S, Goetz S, Dimarco E, De Luca M, Bradshaw RA (2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB J. 14 (7): 973–81. doi:10.1096/fasebj.14.7.973. PMID 10783152. S2CID 43317719.
Wang X, Weng LP, Yu Q (2000). "Specific inhibition of FGF-induced MAPK activation by the receptor-like protein tyrosine phosphatase LAR". Oncogene. 19 (19): 2346–53. doi:10.1038/sj.onc.1203558. PMID 10822386.
Dhalluin C, Yan KS, Plotnikova O, Lee KW, Zeng L, Kuti M, Mujtaba S, Goldfarb MP, Zhou MM (2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell. 6 (4): 921–9. doi:10.1016/S1097-2765(05)00087-0. PMC 5155437. PMID 11090629.
Kao S, Jaiswal RK, Kolch W, Landreth GE (2001). "Identification of the mechanisms regulating the differential activation of the mapk cascade by epidermal growth factor and nerve growth factor in PC12 cells". J. Biol. Chem. 276 (21): 18169–77. doi:10.1074/jbc.M008870200. PMID 11278445.
Ong SH, Hadari YR, Gotoh N, Guy GR, Schlessinger J, Lax I (2001). "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. 98 (11): 6074–9. Bibcode:2001PNAS...98.6074O. doi:10.1073/pnas.111114298. PMC 33424. PMID 11353842.
Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M (2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.
Melillo RM, Santoro M, Ong SH, Billaud M, Fusco A, Hadari YR, Schlessinger J, Lax I (2001). "Docking protein FRS2 links the protein tyrosine kinase RET and its oncogenic forms with the mitogen-activated protein kinase signaling cascade". Mol. Cell. Biol. 21 (13): 4177–87. doi:10.1128/MCB.21.13.4177-4187.2001. PMC 87079. PMID 11390647.
Hadari YR, Gotoh N, Kouhara H, Lax I, Schlessinger J (2001). "Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways". Proc. Natl. Acad. Sci. U.S.A. 98 (15): 8578–83. Bibcode:2001PNAS...98.8578H. doi:10.1073/pnas.161259898. PMC 37478. PMID 11447289.
Yan KS, Kuti M, Yan S, Mujtaba S, Farooq A, Goldfarb MP, Zhou MM (2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. 277 (19): 17088–94. doi:10.1074/jbc.M107963200. PMID 11877385.
Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A (2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6684–9. Bibcode:2002PNAS...99.6684W. doi:10.1073/pnas.052138899. PMC 124463. PMID 11997436.
Stoletov KV, Ratcliffe KE, Terman BI (2002). "Fibroblast growth factor receptor substrate 2 participates in vascular endothelial growth factor-induced signaling". FASEB J. 16 (10): 1283–5. doi:10.1096/fj.01-0835fje. PMID 12154000. S2CID 35161062.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리즈 89: ENSG00000166225 - 앙상블, 2017년 5월

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Rabin SJ, Cleghon V, Kaplan DR (April 1993). "SNT, a differentiation-specific target of neurotrophic factor-induced tyrosine kinase activity in neurons and PC12 cells". Molecular and Cellular Biology. 13 (4): 2203–13. doi:10.1128/mcb.13.4.2203. PMC 359541. PMID 7681142.

[pmid8761293-5] Wang JK, Xu H, Li HC, Goldfarb M (October 1996). "Broadly expressed SNT-like proteins link FGF receptor stimulation to activators of Ras". Oncogene. 13 (4): 721–9. PMID 8761293.

[pmid9660748-6] Xu H, Lee KW, Goldfarb M (August 1998). "Novel recognition motif on fibroblast growth factor receptor mediates direct association and activation of SNT adapter proteins". J Biol Chem. 273 (29): 17987–90. doi:10.1074/jbc.273.29.17987. PMID 9660748.

[7] "Entrez Gene: FRS2 Fibroblast growth factor receptor substrate 2".

[8] Pawson T, Scott JD (December 1997). "Signaling through scaffold, anchoring, and adaptor proteins". Science. 278 (5346): 2075–80. Bibcode:1997Sci...278.2075P. doi:10.1126/science.278.5346.2075. PMID 9405336.

[9] Valencia T, Joseph A, Kachroo N, Darby S, Meakin S, Gnanapragasam VJ (Nov 11, 2011). "Role and expression of FRS2 and FRS3 in prostate cancer". BMC Cancer. 11: 484. doi:10.1186/1471-2407-11-484. PMC 3231952. PMID 22078327.

[10] Chen Y, McGee J, Chen X, Doman TN, Gong X, Zhang Y, Hamm N, Ma X, Higgs RE, Bhagwat SV, Buchanan S, Peng SB, Staschke KA, Yadav V, Yue Y, Kouros-Mehr H (2014). "Identification of Druggable Cancer Driver Genes Amplified across TCGA Datasets". PLOS ONE. 9 (5): e98293. Bibcode:2014PLoSO...998293C. doi:10.1371/journal.pone.0098293. PMC 4038530. PMID 24874471.

[pmid11997436-11] Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A (May 2002). "FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6684–9. Bibcode:2002PNAS...99.6684W. doi:10.1073/pnas.052138899. PMC 124463. PMID 11997436.

[pmid11877385-12] Yan KS, Kuti M, Yan S, Mujtaba S, Farooq A, Goldfarb MP, Zhou MM (May 2002). "FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors". J. Biol. Chem. 277 (19): 17088–94. doi:10.1074/jbc.M107963200. PMID 11877385.

[pmid10629055-13] Ong SH, Guy GR, Hadari YR, Laks S, Gotoh N, Schlessinger J, Lax I (February 2000). "FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors". Mol. Cell. Biol. 20 (3): 979–89. doi:10.1128/mcb.20.3.979-989.2000. PMC 85215. PMID 10629055.

[pmid11090629-14] Dhalluin C, Yan KS, Plotnikova O, Lee KW, Zeng L, Kuti M, Mujtaba S, Goldfarb MP, Zhou MM (October 2000). "Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors". Mol. Cell. 6 (4): 921–9. doi:10.1016/S1097-2765(05)00087-0. PMC 5155437. PMID 11090629.

[pmid8780727-15] Ong SH, Goh KC, Lim YP, Low BC, Klint P, Claesson-Welsh L, Cao X, Tan YH, Guy GR (August 1996). "Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochem. Biophys. Res. Commun. 225 (3): 1021–6. doi:10.1006/bbrc.1996.1288. PMID 8780727.

[pmid10092678-16] Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM (April 1999). "The signaling adapter FRS-2 competes with Shc for binding to the nerve growth factor receptor TrkA. A model for discriminating proliferation and differentiation". J. Biol. Chem. 274 (14): 9861–70. doi:10.1074/jbc.274.14.9861. PMID 10092678.

[pmid9182757-17] Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J (May 1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell. 89 (5): 693–702. doi:10.1016/s0092-8674(00)80252-4. PMID 9182757. S2CID 2187363.

[pmid10383403-18] Lim YP, Low BC, Lim J, Wong ES, Guy GR (July 1999). "Association of atypical protein kinase C isotypes with the docker protein FRS2 in fibroblast growth factor signaling". J. Biol. Chem. 274 (27): 19025–34. doi:10.1074/jbc.274.27.19025. PMID 10383403.

[pmid10650943-19] Delahaye L, Rocchi S, Van Obberghen E (February 2000). "Potential involvement of FRS2 in insulin signaling". Endocrinology. 141 (2): 621–8. doi:10.1210/endo.141.2.7298. PMID 10650943.

[pmid11360177-20] Kurokawa K, Iwashita T, Murakami H, Hayashi H, Kawai K, Takahashi M (April 2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene. 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.

[pmid9632781-21] Hadari YR, Kouhara H, Lax I, Schlessinger J (July 1998). "Binding of Shp2 tyrosine phosphatase to FRS2 is essential for fibroblast growth factor-induced PC12 cell differentiation". Mol. Cell. Biol. 18 (7): 3966–73. doi:10.1128/mcb.18.7.3966. PMC 108981. PMID 9632781.

[pmid10783152-22] Foehr ED, Tatavos A, Tanabe E, Raffioni S, Goetz S, Dimarco E, De Luca M, Bradshaw RA (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB J. 14 (7): 973–81. doi:10.1096/fasebj.14.7.973. PMID 10783152. S2CID 43317719.

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