FLT3(FMS-like tyrosine kinase 3)是一种属于III型受体酪氨酸激酶(RTK)家族的基因,该家族还包括KIT、PDGFR等成员,它们共同特点是具有细胞外配体结合域、跨膜域和细胞内酪氨酸激酶域,主要参与细胞增殖、分化和存活信号的传导。FLT3主要在造血干细胞和祖细胞中表达,其配体FLT3L(FLT3配体)结合后激活下游信号通路(如RAS/MAPK、PI3K/AKT和STAT5),对造血系统的发育和免疫细胞生成至关重要。FLT3基因突变(尤其是内部串联重复突变FLT3-ITD和酪氨酸激酶结构域点突变FLT3-TKD)会导致激酶持续激活,与急性髓系白血病(AML)密切相关,这类患者预后较差。FLT3-ITD突变通过异常激活增殖信号并抑制分化,促进白血病发生。FLT3过表达会增强造血前体细胞的自我更新能力,可能导致骨髓增殖异常;而表达降低则可能损害造血干细胞池的维持和免疫细胞生成。针对FLT3突变的靶向药物(如米哚妥林、吉瑞替尼)已用于AML治疗。FLT3基因家族成员在肿瘤发生、干细胞调控中具有重要作用,其异常激活常与血液系统恶性肿瘤相关。
This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]
这个基因编码,调节造血Ⅲ类受体酪氨酸激酶。这种受体是通过对细胞外结构域,其诱导在质膜,导致受体的自磷酸化同二聚体形成FMS相关酪氨酸激酶3配体的结合而活化。活化的受体激酶随后磷酸化并在参与细胞凋亡,增殖,和在骨髓造血细胞的分化途径激活多种细胞质效应分子。导致在急性骨髓性白血病和急性淋巴细胞性白血病该受体结果的组成性活化的突变。 [由RefSeq的,2015年1月提供]
FLT3基因(以及对应的蛋白质)的细胞分布位置:
FLT3基因的本体(GO)信息:
名称 |
---|
4060 Cytokine-cytokine receptor interaction [PATH:hsa04060] |
4640 Hematopoietic cell lineage [PATH:hsa04640] |
5200 Pathways in cancer [PATH:hsa05200] |
5230 Central carbon metabolism in cancer [PATH:hsa05230] |
5202 Transcriptional misregulation in cancers [PATH:hsa05202] |
5221 Acute myeloid leukemia [PATH:hsa05221] |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
Leukemia, Myelocytic, Acute | 0.56 | 707 | 10 | BeFree_CLINVAR_CTD_human_GAD_LHGDN_MGD |
Acute Promyelocytic Leukemia | 0.146588829 | 46 | 0 | BeFree_CTD_human_GAD_LHGDN |
Acute lymphocytic leukemia | 0.130314791 | 38 | 3 | BeFree_CLINVAR |
Acute biphenotypic leukemia | 0.12 | 0 | 0 | ORPHANET |
Thrombosis | 0.12 | 1 | 0 | CTD_human |
LEUKEMIA, ACUTE LYMPHOBLASTIC, SUSCEPTIBILITY TO, 3 | 0.12 | 0 | 0 | ORPHANET |
leukemia | 0.093278617 | 151 | 1 | BeFree_GAD_LHGDN |
Juvenile Myelomonocytic Leukemia | 0.080542884 | 2 | 0 | BeFree_MGD |
Arthritis, Experimental | 0.08 | 1 | 0 | RGD |
Myeloid Leukemia | 0.056970589 | 30 | 1 | BeFree_GAD_LHGDN |
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