cDNA cloning and characterization of human monocyte/macrophage serine esterase-1

Abstract

Human monocyte/macrophage serine esterase (HMSE), commonly known as acid esterase or alpha-naphthylacetate esterase, comprises a group of five enzyme variants that can be distinguished by their isoelectric points from esterase variants of the other normal human blood cell populations. A cDNA for one of the monocytic enzyme variants (HMSE1) was cloned from a U-937 lambda gt11 cDNA library by screening with an oligonucleotide mixture designed according to amino acid sequence data of the purified enzyme. The cDNA contains 1,727 bp with an open reading frame of 1,512 bp coding for a protein of 503 amino acid residues. HMSE1 cDNA represents the first cloned monocyte/macrophage-specific serine esterase and its sequence shows up to 77% homology to other known serine esterases of different species. The amino acid composition of the putative active site of HMSE1 as deduced from the nucleotide sequence corresponds with the active sites of other serine esterases but not with the active sites of serine proteases. Hybridization of the cDNA with RNA of separated normal blood cell populations and hematopoietic cell lines shows restricted expression within the monocyte/macrophage lineage.

Structure and Catalytic Properties of Carboxylesterase Isozymes Involved in Metabolic Activation of Prodrugs

“…Most of all CES1 family, except CES1G, are mainly expressed in liver. The CES 1A subfamily includes the major forms of human, monkey and rabbit CES, and the CES1B includes the major isoforms of rat, mouse and hamster CES, and CES1C includes the major isoforms of dog, cat and pig CES [ 1 , 4 , 5 , 23 , 40 , 46 , 57 , 58 , 59 , 60 ]. The CES 1H subfamily includes CES RL1 (CES1H4), mouse ES 4(Ces1H1) and Hydrolase B (CES1H3) and C (CES1H2), which catalyze long-chain acyl-CoA hydrolysis [ 3 , 4 , 10 , 22 , 25 , 61 ].…”

“…Therefore, the organization of the CES gene is evolutionarily conserved in mice and humans. In previous studies, the human CES gene have been mapped to chromosome 16 at 16q13–q22.1 [ 18 , 57 ]. This region is syntenic to a region of mouse chromosome 8 at 8C5 [ 57 ].…”

Nonspecific esterase released from thymic macrophages accumulates in the apoptotic thymocytes: an indication for this enzyme participating in the clearance of apoptotic thymocytes

“…Some in early studies argued that NSE was localized in the endoplasmic reticulum, while others argued that NSE was on the plasma membrane. Recently, the amino acid sequence inferred from the NSE cDNA clone showing the presence of a putative short transmembrane sequence comprising 17 amino acids 7, 11 is consistent with both possibilities. Our observations suggest that NSE is a mobile enzyme, the subcellular localization of which changes according to different situations, thereby reconciling the findings in different studies.…”

“…In contrast to granulocytic esterase, macrophage specific NSE is sensitive to sodium fluoride (NaF) and disopropyl fluorophosphates (DFP), suggesting the presence of a serine in its active site 7. In humans, a cDNA clone (HMSE1) encoding NSE has been sequenced and a computer analysis has confirmed the existence of a catalytic active serine 8. The biological function of the NSE is still unclear.…”

Selection of down‐regulated sequences along the monocytic differentiation of leukemic HL60 cells

“…The isolation of several HL60 and U937 TPA‐resistant variants allowed the characterisation of essential regulators such as different protein kinase C isoforms [9, 10]. Furthermore, analyses of gene expression modulations by cDNA differential screening have lead to the identification of some molecules including the transcription factor Erg‐1 [11], the Mpg‐1 protein [12]or the monocyte serine esterase‐1 [13], the expressions of which are enhanced along monocytic differentiation.…”