B 셀 링커

BLNK
사용 가능한 구조
PDB	Ortholog 검색: PDBe RCSB
PDB ID 코드 목록
	2EO6
식별자
에일리어스	BLNK, AGM4, BASH, BLNK-S, LY57, SLP-65, SLP65, bca, B셀링커, B셀링커
외부 ID	OMIM: 604515 MGI: 96878 HomoloGene: 32038 GeneCard: BLNK
유전자 위치(인간)
크르.	10번 염색체(인간)
끝.	96,271,587 bp
유전자 위치(마우스)
크르.	19번 염색체(쥐)
끝.	40,982,978 bp
RNA발현패턴
	상단 표시 위치:
	구강; ; 부고환 말뭉치; ; 비장; ; 제주날 점막; ; 십이지장; ; 부록; ; 림프절; ; 간우엽; ; 잇몸; ; 흉선;
	추가 참조 표현식 데이터
	추가 참조 표현식 데이터
유전자 존재론
분자 함수	막관통수용체단백질티로신인산화효소어댑터활성; GO:0001948 단백질 결합;
셀룰러 컴포넌트	세포; 막; 세포질; 세포내 해부학적 구조; 혈장막; 세포질 리보핵단백질과립;
생물학적 과정	체액성 면역 반응; B세포분화; GO:0007243 세포내 신호 전달; B세포활성화; 염증 반응; 신호 전달의 양성 조절; 막간수용체단백질티로신인산화효소신호전달경로;
	출처:아미고 / QuickGO
맞춤법
	29760
	17060
	ENSG000095585
	ENSMUSG00000061132
	Q8WV28
	Q9QUN3
	NM_001114094; NM_001258440; NM_001258441; NM_001258442; NM_013314
	NM_008528; NM_001365054
	NP_001107566; NP_001245369; NP_001245370; NP_001245371; NP_037446
	NP_032554; NP_001351983
	위키데이터
인간 보기/편집	마우스 표시/편집

B세포 링커 단백질은 BLNK 유전자에^[5]^[6] 의해 암호화되며 SLP-65,^[7] ^[8]BASH 및 ^[9]BCA로도 알려진 어댑터 단백질이다.BLNK는 B세포 및 대식세포에서 발현되며, 그 패러로그 SLP-76이 T세포 수용체 ^[10]시그널링에서 수행하는 역할과 유사한 방식으로 B세포 수용체 시그널링에서 큰 역할을 한다.BLNK는 알려진 내인성 효소 활성이 없기 때문에 B세포 수용체 하류의 신호전달 효과인자를 시간적, 공간적으로 배위 및 조절하는 기능을 한다.

기능.

BLNK의 기능은 BLNK 결핍 DT40 세포에서 처음 설명되었으며, 닭 B 세포군은 폐기된 세포 내 칼슘 동원 반응과 MAP 키나아제 p38, JNK의 활성 저하를 나타냈으며, B세포 수용체(BCR)의 활성은 DT에 비해 낮은 수준이다.녹아웃 마우스에서는 BLNK 결핍이 B세포 ^[12]^[13]발달의 부분적인 차단으로 이어지고, 인간에서는 BLNK 결핍이 B세포 ^[14]발달의 훨씬 더 심오한 차단으로 이어진다.

링커 또는 어댑터 단백질은 수용체가 하류 이펙터 단백질을 증폭하고 조절할 수 있는 메커니즘을 제공합니다.B세포 링커 단백질은 정상적인 B세포 발달에 필수적이다.[OMIM ^[6]제공]

구조.

BLNK는 N 말단 류신 지퍼 모티브에 이어 "산성" 영역, 프롤린이 풍부한 영역 및 C 말단 SH2 도메인으로 구성됩니다.류신 지퍼 모티브는 BLNK가 막 ^[15]단백질과의 코일-코일 상호작용에 의해 혈장 막에 위치할 수 있도록 합니다.이 류신 지퍼 모티브는 BLNK와 류신과 이소류신 잔기의 N 말단 헵타드 유사 조직을 가지고 있지만 실험적으로 이 모티브를 가지고 있음이 증명되지 않은 패러로그 SLP-76을 구별한다.또한 BLNK의 SH2 도메인을 B세포 수용체 ^[16]^[17]^[18]복합체의 일부인 Igα에서 비ITAM 포스포티로신에 결합함으로써 혈장막으로의 BLNK의 신원이 달성된다.

BLNK의 산성 영역에는 BLNK와 PLC,2, Btk, Vav ^[19]및 Nck 사이의 단백질-단백질 상호작용을 매개하는 유도 인산화 티로신 잔기가 몇 개 포함되어 있다.DT40 세포에서 BLNK에 대한 보다 최근의 질량 분석 연구는 적어도 41개의 고유한 세린, 트레오닌 및 티로신 잔기가 BLNK에서 ^[20]인산화된다는 것을 발견했다.

상호 작용

B세포 링커는 Grb2,^[5]^[7]^[16]^[21] SH3KBP1,^[22] CD79A,^[16]^[17] MAP4K1^[23] 및 브루톤의 티로신 ^[24]^[25]키나제와 상호작용하는 것으로 나타났다.

번역 후 수정

레퍼런스

^ ^a ^b ^c GRCh38: 앙상블 릴리즈 89: ENSG000095585 - 앙상블, 2017년 5월
^ ^a ^b ^c GRCm38: 앙상블 릴리즈 89: ENSMUSG000061132 - 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.
^ ^a ^b Fu, C.; Turck, C. W.; Kurosaki, T.; Chan, A. C. (1998). "BLNK: A central linker protein in B cell activation". Immunity. 9 (1): 93–103. doi:10.1016/S1074-7613(00)80591-9. PMID 9697839.
^ ^a ^b "Entrez Gene: BLNK B-cell linker".
^ ^a ^b Wienands, J.; Schweikert, J.; Wollscheid, B.; Jumaa, H.; Nielsen, P. J.; Reth, M. (1998). "SLP-65: A new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation". The Journal of Experimental Medicine. 188 (4): 791–795. doi:10.1084/jem.188.4.791. PMC 2213353. PMID 9705962.
^ Goitsuka, R.; Fujimura, Y.; Mamada, H.; Umeda, A.; Morimura, T.; Uetsuka, K.; Doi, K.; Tsuji, S.; Kitamura, D. (1998). "BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius". Journal of Immunology. 161 (11): 5804–5808. PMID 9834055.
^ Gangi-Peterson, L.; Peterson, S. N.; Shapiro, L. H.; Golding, A.; Caricchio, R.; Cohen, D. I.; Margulies, D. H.; Cohen, P. L. (1998). "Bca: An activation-related B-cell gene". Molecular Immunology. 35 (1): 55–63. doi:10.1016/s0161-5890(98)00008-x. PMID 9683264.
^ Koretzky, G. A.; Abtahian, F.; Silverman, M. A. (2006). "SLP76 and SLP65: Complex regulation of signalling in lymphocytes and beyond". Nature Reviews Immunology. 6 (1): 67–78. doi:10.1038/nri1750. PMID 16493428. S2CID 22368341.
^ Ishiai, M.; Kurosaki, M.; Pappu, R.; Okawa, K.; Ronko, I.; Fu, C.; Shibata, M.; Iwamatsu, A.; Chan, A. C.; Kurosaki, T. (1999). "BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells". Immunity. 10 (1): 117–125. doi:10.1016/S1074-7613(00)80012-6. PMID 10023776.
^ Jumaa, H.; Wollscheid, B.; Mitterer, M.; Wienands, J.; Reth, M.; Nielsen, P. J. (1999). "Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65". Immunity. 11 (5): 547–554. doi:10.1016/S1074-7613(00)80130-2. PMID 10591180.
^ Pappu, R.; Cheng, A. M.; Li, B.; Gong, Q.; Chiu, C.; Griffin, N.; White, M.; Sleckman, B. P.; Chan, A. C. (1999). "Requirement for B cell linker protein (BLNK) in B cell development". Science. 286 (5446): 1949–1954. doi:10.1126/science.286.5446.1949. PMID 10583957.
^ Minegishi, Y.; Rohrer, J.; Coustan-Smith, E.; Lederman, H. M.; Pappu, R.; Campana, D.; Chan, A. C.; Conley, M. E. (1999). "An essential role for BLNK in human B cell development". Science. 286 (5446): 1954–1957. doi:10.1126/science.286.5446.1954. PMID 10583958.
^ Köhler, F.; Storch, B.; Kulathu, Y.; Herzog, S.; Kuppig, S.; Reth, M.; Jumaa, H. (2005). "A leucine zipper in the N terminus confers membrane association to SLP-65". Nature Immunology. 6 (2): 204–210. doi:10.1038/ni1163. PMID 15654340. S2CID 10708737.
^ ^a ^b ^c Engels, N.; Wollscheid, B.; Wienands, J. R. (2001). "Association of SLP-65 / BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-α". European Journal of Immunology. 31 (7): 2126–2134. doi:10.1002/1521-4141(200107)31:7<2126::AID-IMMU2126>3.0.CO;2-O. PMID 11449366.
^ ^a ^b Kabak, S.; Skaggs, B. J.; Gold, M. R.; Affolter, M.; West, K. L.; Foster, M. S.; Siemasko, K.; Chan, A. C.; Aebersold, R.; Clark, M. R. (2002). "The Direct Recruitment of BLNK to Immunoglobulin α Couples the B-Cell Antigen Receptor to Distal Signaling Pathways". Molecular and Cellular Biology. 22 (8): 2524–2535. doi:10.1128/MCB.22.8.2524-2535.2002. PMC 133735. PMID 11909947.
^ Pike, K. A.; Ratcliffe, M. J. (2005). "Dual requirement for the Ig alpha immunoreceptor tyrosine-based activation motif (ITAM) and a conserved non-Ig alpha ITAM tyrosine in supporting Ig alpha beta-mediated B cell development". Journal of Immunology. 174 (4): 2012–2020. doi:10.4049/jimmunol.174.4.2012. PMID 15699130.
^ Chiu, C. W.; Dalton, M.; Ishiai, M.; Kurosaki, T.; Chan, A. C. (2002). "BLNK: Molecular scaffolding through 'cis'-mediated organization of signaling proteins". The EMBO Journal. 21 (23): 6461–6472. doi:10.1093/emboj/cdf658. PMC 136961. PMID 12456653.
^ Oellerich, T.; Gronborg, M.; Neumann, K.; Hsiao, H. -H.; Urlaub, H.; Wienands, J. (2009). "SLP-65 Phosphorylation Dynamics Reveals a Functional Basis for Signal Integration by Receptor-proximal Adaptor Proteins". Molecular & Cellular Proteomics. 8 (7): 1738–1750. doi:10.1074/mcp.M800567-MCP200. PMC 2709198. PMID 19372136.
^ Fusaki, N.; Tomita, S.; Wu, Y.; Okamoto, N.; Goitsuka, R.; Kitamura, D.; Hozumi, N. (2000). "BLNK is associated with the CD72 / SHP-1 / Grb2 complex in the WEHI231 cell line after membrane IgM cross-linking". European Journal of Immunology. 30 (5): 1326–1330. doi:10.1002/(SICI)1521-4141(200005)30:5<1326::AID-IMMU1326>3.0.CO;2-Q. PMID 10820378.
^ Watanabe, S.; Take, H.; Takeda, K.; Yu, Z. X.; Iwata, N.; Kajigaya, S. (2000). "Characterization of the CIN85 Adaptor Protein and Identification of Components Involved in CIN85 Complexes". Biochemical and Biophysical Research Communications. 278 (1): 167–174. doi:10.1006/bbrc.2000.3760. PMID 11071869.
^ Tsuji, S.; Okamoto, M.; Yamada, K.; Okamoto, N.; Goitsuka, R.; Arnold, R.; Kiefer, F.; Kitamura, D. (2001). "B Cell Adaptor Containing Src Homology 2 Domain (Bash) Links B Cell Receptor Signaling to the Activation of Hematopoietic Progenitor Kinase 1". The Journal of Experimental Medicine. 194 (4): 529–539. doi:10.1084/jem.194.4.529. PMC 2193495. PMID 11514608.
^ Yasuda, T.; Tezuka, T.; Maeda, A.; Inazu, T.; Yamanashi, Y.; Gu, H.; Kurosaki, T.; Yamamoto, T. (2002). "Cbl-b Positively Regulates Btk-mediated Activation of Phospholipase C-γ2 in B Cells". The Journal of Experimental Medicine. 196 (1): 51–63. doi:10.1084/jem.20020068. PMC 2194016. PMID 12093870.
^ Hashimoto, S.; Iwamatsu, A.; Ishiai, M.; Okawa, K.; Yamadori, T.; Matsushita, M.; Baba, Y.; Kishimoto, T.; Kurosaki, T.; Tsukada, S. (1999). "Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling". Blood. 94 (7): 2357–2364. doi:10.1182/blood.V94.7.2357.419k40_2357_2364. PMID 10498607.

추가 정보

Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Fu C, Chan AC (1997). "Identification of two tyrosine phosphoproteins, pp70 and pp68, which interact with phospholipase Cgamma, Grb2, and Vav after B cell antigen receptor activation". J. Biol. Chem. 272 (43): 27362–8. doi:10.1074/jbc.272.43.27362. PMID 9341187.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Wienands J, Schweikert J, Wollscheid B, et al. (1998). "SLP-65: a new signaling component in B lymphocytes that requires expression of the antigen receptor for phosphorylation". J. Exp. Med. 188 (4): 791–5. doi:10.1084/jem.188.4.791. PMC 2213353. PMID 9705962.
Hashimoto S, Iwamatsu A, Ishiai M, et al. (1999). "Identification of the SH2 domain binding protein of Bruton's tyrosine kinase as BLNK--functional significance of Btk-SH2 domain in B-cell antigen receptor-coupled calcium signaling". Blood. 94 (7): 2357–64. doi:10.1182/blood.V94.7.2357.419k40_2357_2364. PMID 10498607.
Su YW, Zhang Y, Schweikert J, et al. (1999). "Interaction of SLP adaptors with the SH2 domain of Tec family kinases". Eur. J. Immunol. 29 (11): 3702–11. doi:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R. PMID 10556826.
Fusaki N, Tomita S, Wu Y, et al. (2000). "BLNK is associated with the CD72/SHP-1/Grb2 complex in the WEHI231 cell line after membrane IgM cross-linking". Eur. J. Immunol. 30 (5): 1326–30. doi:10.1002/(SICI)1521-4141(200005)30:5<1326::AID-IMMU1326>3.0.CO;2-Q. PMID 10820378.
Mizuno K, Tagawa Y, Mitomo K, et al. (2000). "Src homology region 2 (SH2) domain-containing phosphatase-1 dephosphorylates B cell linker protein/SH2 domain leukocyte protein of 65 kDa and selectively regulates c-Jun NH2-terminal kinase activation in B cells". J. Immunol. 165 (3): 1344–51. doi:10.4049/jimmunol.165.3.1344. PMID 10903736.
Guo B, Kato RM, Garcia-Lloret M, et al. (2000). "Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex". Immunity. 13 (2): 243–53. doi:10.1016/S1074-7613(00)00024-8. PMID 10981967.
Watanabe S, Take H, Takeda K, et al. (2001). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochem. Biophys. Res. Commun. 278 (1): 167–74. doi:10.1006/bbrc.2000.3760. PMID 11071869.
Tan JE, Wong SC, Gan SK, et al. (2001). "The adaptor protein BLNK is required for b cell antigen receptor-induced activation of nuclear factor-kappa B and cell cycle entry and survival of B lymphocytes". J. Biol. Chem. 276 (23): 20055–63. doi:10.1074/jbc.M010800200. PMID 11274146.
Adachi T, Wienands J, Wakabayashi C, et al. (2001). "SHP-1 requires inhibitory co-receptors to down-modulate B cell antigen receptor-mediated phosphorylation of cellular substrates". J. Biol. Chem. 276 (28): 26648–55. doi:10.1074/jbc.M100997200. PMID 11356834.
Engels N, Wollscheid B, Wienands J (2001). "Association of SLP-65/BLNK with the B cell antigen receptor through a non-ITAM tyrosine of Ig-alpha". Eur. J. Immunol. 31 (7): 2126–34. doi:10.1002/1521-4141(200107)31:7<2126::AID-IMMU2126>3.0.CO;2-O. PMID 11449366.
Sauer K, Liou J, Singh SB, et al. (2002). "Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes". J. Biol. Chem. 276 (48): 45207–16. doi:10.1074/jbc.M106811200. PMID 11487585.
Engels N, Merchant M, Pappu R, et al. (2001). "Epstein-Barr virus latent membrane protein 2A (LMP2A) employs the SLP-65 signaling module". J. Exp. Med. 194 (3): 255–64. doi:10.1084/jem.194.3.255. PMC 2193464. PMID 11489945.
Tsuji S, Okamoto M, Yamada K, et al. (2001). "B cell adaptor containing src homology 2 domain (BASH) links B cell receptor signaling to the activation of hematopoietic progenitor kinase 1". J. Exp. Med. 194 (4): 529–39. doi:10.1084/jem.194.4.529. PMC 2193495. PMID 11514608.
Kabak S, Skaggs BJ, Gold MR, et al. (2002). "The direct recruitment of BLNK to immunoglobulin alpha couples the B-cell antigen receptor to distal signaling pathways". Mol. Cell. Biol. 22 (8): 2524–35. doi:10.1128/MCB.22.8.2524-2535.2002. PMC 133735. PMID 11909947.
Yasuda T, Tezuka T, Maeda A, et al. (2002). "Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells". J. Exp. Med. 196 (1): 51–63. doi:10.1084/jem.20020068. PMC 2194016. PMID 12093870.

외부 링크

UCSC 게놈 브라우저의 인간 BLNK 게놈 위치 및 BLNK 유전자 세부 정보 페이지.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리즈 89: ENSG000095585 - 앙상블, 2017년 5월

[refGRCm38Ensembl-2] GRCm38: 앙상블 릴리즈 89: ENSMUSG000061132 - 앙상블, 2017년 5월

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

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

[pmid9697839-5] Fu, C.; Turck, C. W.; Kurosaki, T.; Chan, A. C. (1998). "BLNK: A central linker protein in B cell activation". Immunity. 9 (1): 93–103. doi:10.1016/S1074-7613(00)80591-9. PMID 9697839.

[entrez-6] "Entrez Gene: BLNK B-cell linker".

[pmid9705962-7] Wienands, J.; Schweikert, J.; Wollscheid, B.; Jumaa, H.; Nielsen, P. J.; Reth, M. (1998). "SLP-65: A new signaling component in B lymphocytes which requires expression of the antigen receptor for phosphorylation". The Journal of Experimental Medicine. 188 (4): 791–795. doi:10.1084/jem.188.4.791. PMC 2213353. PMID 9705962.

[pmid9834055-8] Goitsuka, R.; Fujimura, Y.; Mamada, H.; Umeda, A.; Morimura, T.; Uetsuka, K.; Doi, K.; Tsuji, S.; Kitamura, D. (1998). "BASH, a novel signaling molecule preferentially expressed in B cells of the bursa of Fabricius". Journal of Immunology. 161 (11): 5804–5808. PMID 9834055.

[pmid9683264-9] Gangi-Peterson, L.; Peterson, S. N.; Shapiro, L. H.; Golding, A.; Caricchio, R.; Cohen, D. I.; Margulies, D. H.; Cohen, P. L. (1998). "Bca: An activation-related B-cell gene". Molecular Immunology. 35 (1): 55–63. doi:10.1016/s0161-5890(98)00008-x. PMID 9683264.

[pmid16493428-10] Koretzky, G. A.; Abtahian, F.; Silverman, M. A. (2006). "SLP76 and SLP65: Complex regulation of signalling in lymphocytes and beyond". Nature Reviews Immunology. 6 (1): 67–78. doi:10.1038/nri1750. PMID 16493428. S2CID 22368341.

[pmid10023776-11] Ishiai, M.; Kurosaki, M.; Pappu, R.; Okawa, K.; Ronko, I.; Fu, C.; Shibata, M.; Iwamatsu, A.; Chan, A. C.; Kurosaki, T. (1999). "BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells". Immunity. 10 (1): 117–125. doi:10.1016/S1074-7613(00)80012-6. PMID 10023776.

[pmid10591180-12] Jumaa, H.; Wollscheid, B.; Mitterer, M.; Wienands, J.; Reth, M.; Nielsen, P. J. (1999). "Abnormal development and function of B lymphocytes in mice deficient for the signaling adaptor protein SLP-65". Immunity. 11 (5): 547–554. doi:10.1016/S1074-7613(00)80130-2. PMID 10591180.

[pmid10583957-13] Pappu, R.; Cheng, A. M.; Li, B.; Gong, Q.; Chiu, C.; Griffin, N.; White, M.; Sleckman, B. P.; Chan, A. C. (1999). "Requirement for B cell linker protein (BLNK) in B cell development". Science. 286 (5446): 1949–1954. doi:10.1126/science.286.5446.1949. PMID 10583957.

[pmid10583958-14] Minegishi, Y.; Rohrer, J.; Coustan-Smith, E.; Lederman, H. M.; Pappu, R.; Campana, D.; Chan, A. C.; Conley, M. E. (1999). "An essential role for BLNK in human B cell development". Science. 286 (5446): 1954–1957. doi:10.1126/science.286.5446.1954. PMID 10583958.

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