Higashihara Masaaki, Watanabe Mariko, Usuda Shigeki, Miyazaki Kouji
Department of Hematology, Internal Medicine, Kitasato University School of Medicine, Sagamihara-shi, Kanagawa 228-8555, Japan.
J Smooth Muscle Res. 2008 Feb;44(1):29-40. doi: 10.1540/jsmr.44.29.
Myosin light chain genes of human hematopoietic cells have not been fully characterized. We previously reported the cloning of the full-length cDNAs of 20 kDa regulatory myosin light chain (MLC-2), named as MLC-2A, from Meg-01, a human megakaryoblastic leukemia cell line (J. Smooth Muscle Res. 37: 25-38, 2001). We now cloned another MLC-2 isoforms from human platelets and U937, a human monocytic leukemia cell line, named as MLC-2B and MLC-2C, respectively. Both MLC-2A and MLC-2B consisted of three exons, which were situated on gene loci 18p1.3. Analysis of the gene structure indicated that MLC-2A and MLC-2B utilized different exons. MLC-2C also consisted of three exons, which was situated on gene loci 20p12. Amino acid sequence of MLC-2C was, of interest, apparently almost the same as that of MLC-2 from chicken gizzard smooth muscle LC20-A (one amino acid's difference) and human vascular smooth muscle LC-20 (two amino acids' difference). All three protein kinase C phosphorylation residues (Ser-1, Ser-2, Thr-9) and both myosin light chain kinase phosporylation residues (Thr-18, Ser-19) are conserved in these three isoforms. The MLC-2A and MLC-2B mRNA were expressed constitutively in all of the human hematopoietic cell lines examined and their expression levels were almost the same. On the other hand, MLC-2C mRNA was expressed in untreated monocytic cell lines (U937 and A-THP-1) and HL-60 differentiated into monocyte/macrophage cell lineage by TPA treatment. These results indicate that smooth muscle type isoform, MLC-2C is the inducible isoform, and might play a crucial role in monocyte/macrophage cell lineage.
人类造血细胞的肌球蛋白轻链基因尚未得到充分表征。我们之前报道过,从人巨核母细胞白血病细胞系Meg-01中克隆出了20 kDa调节性肌球蛋白轻链(MLC-2)的全长cDNA,命名为MLC-2A(《平滑肌研究杂志》37: 25 - 38, 2001)。我们现在又从人血小板和人单核细胞白血病细胞系U937中克隆出了另外两种MLC-2亚型,分别命名为MLC-2B和MLC-2C。MLC-2A和MLC-2B均由三个外显子组成,位于基因座18p1.3上。对基因结构的分析表明,MLC-2A和MLC-2B使用不同的外显子。MLC-2C也由三个外显子组成,位于基因座20p12上。有趣的是,MLC-2C的氨基酸序列与鸡砂囊平滑肌LC20-A的MLC-2(相差一个氨基酸)以及人血管平滑肌LC-20(相差两个氨基酸)几乎相同。这三种亚型中,所有三个蛋白激酶C磷酸化位点(Ser-1、Ser-2、Thr-9)以及两个肌球蛋白轻链激酶磷酸化位点(Thr-18、Ser-19)均保守。MLC-2A和MLC-2B的mRNA在所检测的所有人类造血细胞系中组成性表达,且它们的表达水平几乎相同。另一方面,MLC-2C的mRNA在未经处理的单核细胞系(U937和A-THP-1)以及经佛波酯处理分化为单核细胞/巨噬细胞谱系的HL-60中表达。这些结果表明,平滑肌型亚型MLC-2C是可诱导亚型,可能在单核细胞/巨噬细胞谱系中起关键作用。