GRB2

GRB2（growth factor receptor bound protein 2）は、シグナル伝達に関与するアダプタータンパク質である。ヒトでは、GRB2タンパク質はGRB2遺伝子によってコードされている。 GRB2は上皮成長因子受容体などの受容体に結合するタンパク質で、1つのSH2ドメインと2つのSH3ドメインを有する。2つのSH3ドメインは他のタンパク質のプロリンリッチ領域と直接的に相互作用して複合体形成へ差し向け、SH2ドメインはリン酸化されたチロシンを含む配列に結合する。GRB2遺伝子はCaenorhabditis elegansにおいてシグナル伝達経路に関与しているsem-5遺伝子と類似している。GRB2遺伝子には、異なるアイソフォームをコードする2種類の選択的スプライシングバリアントが発見されている。 GRB2は複数の細胞機能に必要不可欠な役割を果たしている。GRB2の機能の阻害によって、さまざまな生物種で発生過程が損なわれ、またさまざまな細胞種で形質転換や増殖が遮断される。GRB2は上皮成長因子受容体と、Rasやその下流のキナーゼであるERK1/2とを関連づける役割が最もよく知られている。一方で、GRB2はHER2の場合には他のキナーゼAKTに対して関連づける。このように、さまざまな受容体型チロシンキナーゼのシグナルがGRB2へ収束する可能性があるものの、これらのシグナルは必ずしも同じ下流キナーゼの活性化を引き起こすためにGRB2を利用しているわけではない。 GRB2はSH2ドメインの両側にSH3ドメインが隣接した構成をしている。 GRB2のSH2ドメインは、受容体やアダプタータンパク質に存在するリン酸化チロシン（pY）含有モチーフに結合する。pY-X-N-X配列（Xは任意のアミノ酸）に対して選択的に結合するが、pY-(L/V)-N-(V/P)配列に対してより高い親和性で結合する。 N末端側のSH3ドメインはプロリンに富むペプチドに結合し、Rasのグアニンヌクレオチド交換因子であるSos（英語版）に結合することができる。 C末端側のSH3ドメインはP-X-X-X-Rモチーフを有するペプチドに結合し、GAB1（英語版）などのタンパク質への特異的結合を可能にしている。 GRB2は次に挙げる因子と相互作用することが示されている。 ADAM15（英語版） ABL1 ALOX5 BLNK（英語版） BCAR1（英語版） BCR β2AR（英語版） c-Met CBLB（英語版） CD117 CD22（英語版） CD28（英語版） CDKN1B CRK（英語版） CBL CSF1R（英語版） DCTN1（英語版） DNM1（英語版） DOCK1（英語版） DAG1（英語版） EPHA2（英語版） ETV6 EGFR EPOR（英語版） FRS2（英語版） FASL GAB1（英語版） GAB2（英語版） gp130（英語版） G-CSF受容体（英語版） HER2 HNRNPC（英語版） HTT INPP5D（英語版） IRS1 ITK（英語版） JAK1（英語版） JAK2（英語版） KHDRBS1 LAT（英語版） LCP2（英語版） MAP2（英語版） MAP3K1（英語版） MAP4K1（英語版） MED28（英語版） MST1R（英語版） MUC1（英語版） MAPK9（英語版） NCKIPSD（英語版） NEU3（英語版） PDGFRB（英語版） PIK3R1（英語版） PLCG1（英語版） PRKAR1A（英語版） PTK2 PTPN11 PTPN12（英語版） PTPN1（英語版） PTPN6（英語版） PTPRA（英語版） RAPGEF1（英語版） RET SH2B1（英語版） SH3KBP1（英語版） SHC1（英語版） SOS1（英語版） Src SYK（英語版） TNK2（英語版） TrkA（英語版） VAV1（英語版） VAV2（英語版） VAV3（英語版） WASP（英語版） ^ a b c GRCh38: Ensembl release 89: ENSG00000177885 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059923 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ “Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries”. 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