트로포모신수용체키나아제B
Tropomyosin receptor kinase B
트로포미오신 수용체 키나아제 B([5]TrkB)[5]는 타이로신 수용체 키나제 B 또는 BDNF/NT-3 성장인자 수용체 또는 신경퇴행성 티로신 키나제, 수용체, 타입 2는 인간에서 NTRK2 유전자에 의해 인코딩되는 단백질이다.[5][6]TrkB는 뇌에서 유래된 신경영양인자(BDNF)의 수용체다.표준 발음은 "트랙벌"이다.
함수
트로포미오신 수용체 키나아제 B는 여러 '네로트로핀'에 대한 높은 친화력 촉매 수용체로, 이는 구별되는 세포 집단의 생존과 분화를 유도하는 작은 단백질 성장 요인이다.TrkB를 활성화하는 신경트로핀은 BDNF(Brain Departed Neurotrophy Factor), 신경트로핀-4(NT-4), 신경트로핀-3(NT-3)이다.[5]이와 같이 TrkB는 신경 분화와 생존을 포함하는 이러한 신경계통의 여러 가지 효과를 매개한다.연구 결과 TrkB 수용체 활성화가 CNS 세포 내 KCC2 염화물 운반체의 다운 규제로 이어질 수 있는 것으로 나타났다.[7]
TrkB 수용체는 수용체 타이로신 키나아제의 대가족의 일부분이다."tyrosine kinase"는 표적 단백질에 있는 특정 tyrosines, 즉 "기질"에 인산염 그룹을 첨가할 수 있는 효소다.수용체 tyrosine kinase는 세포막에 위치한 "tyrosine kinase"로, 리간드를 수용체의 세포외 영역에 결합시켜 활성화된다.타이로신키나아제 수용체의 다른 예로는 인슐린 수용체, IGF1 수용체, MuSK 단백질 수용체, VEGF 수용체 등이 있다.
현재 포유류 CNS에는 3개의 TrkB 이소폼이 있다.전신 이소폼(TK+)은 대표적인 티로신 키나제 수용체로, Ras-ERK, PI3K, PLCγ 등을 통해 BDNF 신호를 변환한다.대조적으로 잘린 두 개의 이소폼(TK-: T1과 T2)은 TK+와 같은 세포외 영역, 트랜섬브레인 영역, 그리고 처음 12개의 세포내 아미노산 시퀀스를 가지고 있다.단, C-단자 시퀀스는 이소 형태별(각각 11, 9개의 아미노산)이다.T1은 세포 형태학 및 칼슘 유입의 규제에 관여하는 원래의 신호 캐스케이드를 가지고 있다.
가족구성원
TrkB는 TrkA와 TrkC를 포함하는 단백질 키나제 하위 그룹의 일부다.구조적으로 BDNF와 관련된 다른 신경퇴행 요인들이 있다: NGF (신경성장인자의 경우), NT-3 (Neurotropin-3의 경우), NT-4 (Neurotropin-4의 경우).TrkB는 BDNF, NT-4, NT-3의 효과를 매개하는 반면, TrkA는 결합되어 NGF에 의해서만 활성화된다.또한, TrkC는 NT-3에 의해 결합되고 활성화된다.
TrkB는 NT-3보다 BDNF와 NT-4를 더 강력하게 결합한다.TrkC는 TrkB보다 NT-3를 더 강하게 결합한다.
LNGFR
TrkB 외에 다른 BDNF 수용체가 하나 있는데, "LNGFR"("저선호도 신경 성장 인자 수용체"용)이라고 불린다.TrkB와는 달리, LNGFR은 BDNF 생물학에서 다소 덜 명확한 역할을 한다.일부 연구자들은 LNGFR이 신경트로핀의 "싱크" 역할을 한다는 것을 보여주었다.따라서 LNGFR 수용체와 Trk 수용체를 모두 표현하는 세포는 신경트로핀의 "마이크로 농도"가 높기 때문에 더 큰 활성을 가질 수 있다.그러나 LNGFR은 세포가 세포사멸을 통해 죽는 신호를 보낼 수 있다는 것도 밝혀졌으므로, Trk 수용체가 없을 때 LNGFR을 발현하는 세포는 신경트로핀이 있는 곳에서 살기보다는 죽을 수도 있다.
암에서의 역할
Although originally identified as an oncogenic fusion in 1982,[8] only recently has there been a renewed interest in the Trk family as it relates to its role in human cancers because of the identification of NTRK1 (TrkA), NTRK2 (TrkB) and NTRK3 (TrkC) gene fusions and other oncogenic alterations in a number of tumor types.다수의 Trk 억제제는 임상시험에 (2015년) 있으며, 인간 종양의 감소에 있어 초기 가능성을 보여 왔다.[9]
마약 타겟으로
엔트레티닙(옛 RXDX-101)은 이그니타(Ignyta, Inc.)에서 개발한 조사용 약물로, 잠재적 항균작용이 있다.현재 2상 임상시험 중인 trkA, trkB(이 유전자) 및 trkC(존중, NTRK1, NTRK2, NTRK3 유전자로 부호화됨)의 유전자 퓨즈를 대상으로 하는 선택적 범트렉 수용체 tyrosine kinase 억제제(TKI)이다.[10]
리간즈
고민자
- 3,7-디하이드록시플라본
- 3,7,8,2'-테트라하이드록시플라본
- 7,3′-디히드록시플라본
- 7,8,2'-트리히드록시플라본
- 7,8,3'-트리히드록시플라본
- 아미트립티라인[11]
- BNN-20[12]
- 뇌에서 유래된 신경퇴행성인자(BDNF)
- 디옥시게두닌[13]
- 디프레닐
- 디오스메틴
- DMAQ-B1
- 에우트로포플라빈(4'-DMA-7,8-DHF)[14]
- HIOC
- LM22A-4
- N-아세틸세로토닌(NAS)
- 신경트로핀-3 (NT-3)
- 신경트로핀-4 (NT-4)
- 노르웨고닌 (5,7,8-THF)
- R7(트로포플라빈 프로포즈)[15]
- R13(트로포플라빈 프로포즈)[16]
- TDP6
- 트로포플라빈 (7,8-DHF)[17]
반목자
다른이들
상호작용
TrkB는 다음과 상호작용하는 것으로 나타났다.
참고 항목
참조
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Another common feature of neurotrophins is that they produce their physiologic effects by means of the tropomyosin receptor kinase (Trk) receptor family (also known as the tyrosine receptor kinase family). ...Trk receptors All neurotrophins bind to a class of highly homologous receptor tyrosine kinases known as Trk receptors, of which three types are known: TrkA, TrkB, and TrkC. These transmembrane receptors are glycoproteins whose molecular masses range from 140 to 145 kDa. Each type of Trk receptor tends to bind specific neurotrophins: TrkA is the receptor for NGF, TrkB the receptor for BDNF and NT-4, and TrkC the receptor for NT-3.However, some overlap in the specificity of these receptors has been noted.
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추가 읽기
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