ERBB3
小结
ERBB3是原癌基因，编码蛋白是酪氨酸激酶受体（ERBB）家族的成员之一，ERBB3也叫HER3是跨膜受体，ERBB3的独特之处在于它具有有限的激酶活性，比其他家族成员EGFR低约1000倍。ERBB3不能形成同二聚体并且必须与其他ERBB家族成员异二聚化以启动下游信号传导，包括MAPK，PI3K/AKT/mTOR，SRC和STAT途径。ERBB3的过度表达与一些人类癌症中的肿瘤进展和不良预后相关，在胃癌，膀胱癌，子宫癌和结肠直肠癌等肿瘤中检测到ERBB3的体细胞激活突变。
ERBB3 (also HER3) is a transmembrane receptor that is a member of the ERBB family of receptor tyrosine kinases, including EGFR, ERBB2, and ERBB4. ERBB3 is unique in that it has limited kinase activity, approximately 1000 fold less than its family member, EGFR. Thereby, ERBB3 cannot form homodimers and must heterodimerize with other ERBB family members to initiate downstream signaling. Heterodimerization of ERBB3 with its preferred heterodimer partner, ERBB2, results in activation of several signaling pathways, including the MAPK, PI3K/AKT/mTOR, SRC, and STAT pathways. Preclinical models of ERBB2-amplified cancers demonstrate that ERBB2-amplified cells exquisitely rely on ERBB3 to drive proliferation and survival. Moreover, ERBB3 feedback upregulation, localization changes, and ligand overexpression contribute to resistance to ERBB or PI3K/AKT/mTOR inhibitors. Overexpression of ERBB3 has been correlated with tumor progression and poor prognosis in some human cancers. Somatic activating mutations in ERBB3 are found in gastric, bladder, uterine and colorectal cancers, among others.