肝细胞生长因子(HGF)是一种由间质细胞分泌的多功能细胞因子,属于纤溶酶原相关生长因子家族。HGF的主要生物学功能是通过与其受体c-Met(一种酪氨酸激酶受体)结合,激活下游信号通路(如MAPK、PI3K/AKT和STAT),从而调控细胞的增殖、迁移、形态发生和存活。HGF在胚胎发育、组织修复和再生过程中发挥关键作用,尤其在肝脏再生、伤口愈合和血管形成中表现突出。HGF的表达产物是一个异二聚体蛋白,由α链和β链通过二硫键连接而成,具有强烈的促有丝分裂和运动原活性。HGF的主要作用位点包括上皮细胞、内皮细胞和造血干细胞等。HGF基因突变可能导致其功能异常,例如某些突变会削弱与c-Met的结合能力,从而影响组织修复和再生,甚至与肿瘤发生相关。HGF/c-Met信号通路的异常激活与多种癌症(如肝癌、胃癌和乳腺癌)的侵袭和转移密切相关,而该通路的抑制则可能成为抗癌治疗的靶点。HGF过表达会促进细胞迁移和侵袭,可能导致肿瘤转移和血管过度生成;而HGF表达降低则可能影响组织修复能力,导致伤口愈合延迟或器官再生障碍。HGF属于纤溶酶原相关生长因子家族,该家族成员通常具有蛋白酶样结构域,并参与细胞外基质的降解和细胞迁移的调控。家族成员还包括纤溶酶原、巨噬细胞刺激蛋白(MSP)等,它们均通过激活特定的酪氨酸激酶受体来调控细胞行为。HGF在临床上有潜在的应用价值,例如用于促进肝再生或作为缺血性疾病的治疗手段,但其在癌症中的促转移作用也需要警惕。
Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration. It is secreted as a single inactive polypeptide and is cleaved by serine proteases into a 69-kDa alpha-chain and 34-kDa beta-chain. A disulfide bond between the alpha and beta chains produces the active, heterodimeric molecule. The protein belongs to the plasminogen subfamily of S1 peptidases but has no detectable protease activity. Alternative splicing of this gene produces multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
肝细胞生长因子通过激活酪氨酸激酶结合到原癌基因c-Met受体后信号级联调节细胞生长,细胞运动性和形态发生。肝细胞生长因子是由间质细胞和行为分泌作为主要上皮起源的细胞的多官能的细胞因子。其刺激有丝分裂,细胞运动性,并且矩阵侵袭能力使得它在血管生成,肿瘤发生和组织再生中心作用。它被分泌为单个无活性多肽和由丝氨酸蛋白酶裂解成一个69-kDa的阿尔法链和34-kDa的β链。 α和β链间的二硫键产生积极的,异二聚体分子。该蛋白属于S1肽酶的纤维蛋白溶酶原亚科,但没有检测到蛋白酶活性。该基因的可变剪接产生编码不同亚型的多个抄本变形。 [由RefSeq的,2008年7月提供]
HGF基因(以及对应的蛋白质)的细胞分布位置:
HGF基因的本体(GO)信息:
名称 |
---|
4014 Ras signaling pathway [PATH:hsa04014] |
4015 Rap1 signaling pathway [PATH:hsa04015] |
4151 PI3K-Akt signaling pathway [PATH:hsa04151] |
4060 Cytokine-cytokine receptor interaction [PATH:hsa04060] |
4510 Focal adhesion [PATH:hsa04510] |
5200 Pathways in cancer [PATH:hsa05200] |
5205 Proteoglycans in cancer [PATH:hsa05205] |
5218 Melanoma [PATH:hsa05218] |
5211 Renal cell carcinoma [PATH:hsa05211] |
5144 Malaria [PATH:hsa05144] |
名称 |
---|
Cytokine Signaling in Immune system |
Hemostasis |
Immune System |
Interleukin-7 signaling |
Platelet activation, signaling and aggregation |
Platelet degranulation |
Response to elevated platelet cytosolic Ca2+ |
Signaling by Interleukins |
疾病名称 | 关系值 | NofPmids | NofSnps | 来源 |
DEAFNESS, AUTOSOMAL RECESSIVE 39 (disorder) | 0.24 | 0 | 1 | CLINVAR_CTD_human |
Liver carcinoma | 0.144731005 | 63 | 0 | BeFree_CTD_human_LHGDN |
Squamous cell carcinoma | 0.130073144 | 11 | 0 | BeFree_CTD_human_LHGDN |
Liver neoplasms | 0.127881746 | 21 | 0 | BeFree_CTD_human_LHGDN |
Hepatitis, Chronic | 0.126263026 | 6 | 0 | BeFree_CTD_human_LHGDN |
Liver Cirrhosis | 0.125981653 | 14 | 0 | BeFree_CTD_human_LHGDN |
Leukemia, Myelocytic, Acute | 0.123267234 | 3 | 0 | BeFree_CTD_human_LHGDN |
Pulmonary Fibrosis | 0.122985861 | 12 | 0 | BeFree_CTD_human |
Liver Failure, Acute | 0.122171535 | 9 | 0 | BeFree_CTD_human |
Myocardial Ischemia | 0.121628651 | 7 | 0 | BeFree_CTD_human |
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