TRB-1 is a 372 amino acid protein that contains one protein kinase domain and belongs to the Ser/Thr protein kinase superfamily. Expressed ubiquitously with highest expression in bone marrow, thyroid gland, skeletal muscle and pancreas, TRB-1 interacts with MAPK kinases and is thought to regulate the activation of MAP kinses, possibly controlling MAP kinase cascades. The gene encoding TRB-1 maps to human chromosome 8, which consists of nearly 146 million base pairs, houses more than 800 genes and is associated with a variety of diseases and malignancies.
Function:
Interacts with MAPK kinases and regulates activation of MAP kinases. May not display kinase activity.
Subcellular Location:
cytoplasm.
Tissue Specificity:
Expressed in most human tissues with the highest levels in skeletal muscle, thyroid gland, pancreas, peripheral blood leukocytes, and bone marrow.
Similarity:
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Tribbles subfamily.
Contains 1 protein kinase domain.
SWISS:
Q96RU8
Gene ID:
10221
Database links:
Entrez Gene: 10221 Human
Entrez Gene: 211770 Mouse
Entrez Gene: 78969 Rat
Entrez Gene: 521857 Cow
Omim: 609461 Human
SwissProt: Q96RU8 Human
SwissProt: Q8K4K4 Mouse
Unigene: 444947 Human
Unigene: 40298 Mouse
Unigene: 204391 Rat
Trib1在脂肪组织维持和脂质代谢紊乱上发挥关键作用;
巨噬细胞至少有两个亚类,即M1型和M2型。M1型巨噬细胞参与促炎反应,且在宿主防御细菌和病毒感染中发挥核心作用。M2巨噬细胞与抗炎反应、寄生虫感染、组织重构、纤维化以及肿瘤疾病发展相关。 Trib1是个衔接蛋白,与泛素连接酶COP1相互作用参与蛋白降解。人类全基因组关联研究表明TRIB1参与脂质代谢。
日前,大阪大学WPI免疫前沿研究中心等处的研究人员,发现Trib1对F4/80 + MR +组织内在巨噬细胞的分化至关重要,且这些巨噬细胞和M2巨噬细胞、酸性粒细胞具有共同的特性(称之为M2类巨噬细胞)。但是,Trib1在M1髓系细胞就不会发挥这种作用。相关研究成果刊登在近期出版的《自然》(Nature)杂志上。
Trib1缺陷导致各种器官中M2类巨噬细胞急剧减少,如骨髓、脾脏、肺以及脂肪组织。在Trib1缺失的骨髓细胞中,C / EBP α的异常表达要为巨噬细胞分化缺陷负责。没有想到的是,造血细胞缺乏 Trib1的小鼠,减少了脂肪组织块,并伴随着脂肪分解增加,即使是在正常饮食条件下。
M2类巨噬细胞的补充可缓解这种病理学现象。这表明,这类巨噬细胞的缺乏是引发脂肪分解的原因。为了应对高脂肪饮食,造血细胞缺乏 Trib1的小鼠发育中会呈现高甘油三酯血症、胰岛素抗性,同时增加促炎细胞基因诱导。
这些结果表明Trib1在脂肪组织维持和脂质代谢紊乱上发挥关键作用,而其作用是通过控制组织内在M2类巨噬细胞的分化实现的。
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