|
|
 Previous Article | Table of Contents | Next Article 
Organization of the human LU gene and molecular basis of the Lu(a)/Lu(b)
blood group polymorphism
W El Nemer, C Rahuel, Y Colin, P Gane, JP Cartron and C Le Van Kim
INSERM U76, GIP-Institut National de la Transfusion Sanguine, Paris,
France.
The Lutheran (Lu) blood group antigens and the B-cell adhesion molecule
(B-CAM) epithelial cancer antigen are carried by recently cloned integral
glycoproteins that belong to the Ig superfamily. We have previously shown
that the Lu and B-CAM antigens are encoded by the same gene, LU, and that
alternative splicing of the primary transcript most likely accounts for the
presence of both antigens on two isoforms that differ by the length of
their cytoplasmic tails. In the present report, we isolated the human LU
gene by cloning a 20-kb HindIII fragment from Lu(a - b+) genomic DNA. The
LU gene is organized into 15 exons distributed over 12.5 kb. Alternative
splicing of intron 13 generates the 2.5- and 4.0-kb transcript spliceoforms
encoding the long tail and the short tail Lu polypeptides, respectively.
Sequencing of the major mRNA species (2.5 kb) amplified from human bone
marrow, kidney, placenta, and skeletal muscle did not suggest the presence
of tissue- specific Lu glycoprotein isoforms. The same transcription
initiation point, located 22 bp upstream from the initiation codon, was
characterized in several tissues. In agreement with the wide tissue
distribution of the Lu messengers, the GC-rich proximal 5' flanking region
of the LU gene does not contain TATA or CAAT boxes, but includes several
potential binding sites for the ubiquitous Sp1 transcription factor. In
addition, the distal 5' region, encompassing nucleotides - 673 to -764,
contains clustered binding sequences for the GATA, CACCC, and Ets
transcription factors. Analysis of the coding sequences amplified from
genomic DNA of Lu(a + b-) or Lu(a - b+) donors showed a single nucleotide
change in exon 3 (A229G) that correlates with an Aci I restriction site
polymorphism and results in a His77Arg amino-acid substitution. Polymerase
chain reaction/restriction fragment length polymorphism analysis indicated
that the A229G mutation is associated with the Lu(a)/Lu(b) blood group
polymorphism. When expressed in Chinese hamster ovary (CHO) cells, Lu cDNAs
carrying the A229 or the G229 produced cell surface proteins that reacted
with anti-Lu(a) or anti-Lu(b) antibodies, respectively, showing that these
nucleotides specify the Lu(a) and Lu(b) alleles of the Lutheran blood group
locus. CHO cells expressing recombinant short-tail or long-tail Lu
glycoproteins reacted as well with anti-Lu as with anti-B-CAM antibodies,
providing the definitive proof that the Lu blood group and B-CAM antigens
are carried by the same molecules.
Volume 89,
Issue 12,
pp. 4608-4616,
06/15/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. Q. Zeng, Z. H. Deng, B. C. Yang, Y. L. Liang, Y. Q. Su, D. C. Li, and Q. Yu
Polymorphic Analysis of the Lutheran Blood Group System in Chinese
Ann. Clin. Lab. Sci.,
January 1, 2009;
39(1):
38 - 42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. K. Singleton, N. M. Burton, C. Green, R. L. Brady, and D. J. Anstee
Mutations in EKLF/KLF1 form the molecular basis of the rare blood group In(Lu) phenotype
Blood,
September 1, 2008;
112(5):
2081 - 2088.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Vainionpaa, Y. Kikkawa, K. Lounatmaa, J. H. Miner, P. Rousselle, and I. Virtanen
Laminin-10 and Lutheran blood group glycoproteins in adhesion of human endothelial cells
Am J Physiol Cell Physiol,
March 1, 2006;
290(3):
C764 - C775.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Gauthier, C. Rahuel, M. P. Wautier, W. El Nemer, P. Gane, J. L. Wautier, J. P. Cartron, Y. Colin, and C. Le Van Kim
Protein Kinase A-dependent Phosphorylation of Lutheran/Basal Cell Adhesion Molecule Glycoprotein Regulates Cell Adhesion to Laminin {alpha}5
J. Biol. Chem.,
August 26, 2005;
280(34):
30055 - 30062.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Nicolas, C. Le Van Kim, P. Gane, C. Birkenmeier, J.-P. Cartron, Y. Colin, and I. Mouro-Chanteloup
Rh-RhAG/Ankyrin-R, a New Interaction Site between the Membrane Bilayer and the Red Cell Skeleton, Is Impaired by Rhnull-associated Mutation
J. Biol. Chem.,
July 3, 2003;
278(28):
25526 - 25533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Kikkawa, C. L. Moulson, I. Virtanen, and J. H. Miner
Identification of the Binding Site for the Lutheran Blood Group Glycoprotein on Laminin alpha 5 through Expression of Chimeric Laminin Chains in Vivo
J. Biol. Chem.,
November 15, 2002;
277(47):
44864 - 44869.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Mouro-Chanteloup, A. M. D'Ambrosio, P. Gane, C. Le Van Kim, V. Raynal, D. Dhermy, J.-P. Cartron, and Y. Colin
Cell-surface expression of RhD blood group polypeptide is posttranscriptionally regulated by the RhAG glycoprotein
Blood,
July 18, 2002;
100(3):
1038 - 1047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. V. Shusta, R. J. Boado, and W. M. Pardridge
Vascular Proteomics and Subtractive Antibody Expression Cloning
Mol. Cell. Proteomics,
January 1, 2002;
1(1):
75 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. F. Parsons, G. Lee, F. A. Spring, T.-N. Willig, L. L. Peters, J. A. Gimm, M. J. A. Tanner, N. Mohandas, D. J. Anstee, and J. A. Chasis
Lutheran blood group glycoprotein and its newly characterized mouse homologue specifically bind {alpha}5 chain-containing human laminin with high affinity
Blood,
January 1, 2001;
97(1):
312 - 320.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. El Nemer, Y. Colin, C. Bauvy, P. Codogno, R. H. Fraser, J. P. Cartron, and C. L. Van Kim
Isoforms of the Lutheran/Basal Cell Adhesion Molecule Glycoprotein Are Differentially Delivered in Polarized Epithelial Cells. MAPPING OF THE BASOLATERAL SORTING SIGNAL TO A CYTOPLASMIC DI-LEUCINE MOTIF
J. Biol. Chem.,
November 5, 1999;
274(45):
31903 - 31908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J.G. Southcott, M. J.A. Tanner, and D. J. Anstee
The Expression of Human Blood Group Antigens During Erythropoiesis in a Cell Culture System
Blood,
June 15, 1999;
93(12):
4425 - 4435.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. E. Nemer, P. Gane, Y. Colin, V. Bony, C. Rahuel, F. Galacteros, J. P. Cartron, and C. L. Van Kim
The Lutheran Blood Group Glycoproteins, the Erythroid Receptors for Laminin, Are Adhesion Molecules
J. Biol. Chem.,
July 3, 1998;
273(27):
16686 - 16693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. El Nemer, P. Gane, Y. Colin, A. M. D'Ambrosio, I. Callebaut, J.-P. Cartron, and C. L. Van Kim
Characterization of the Laminin Binding Domains of the Lutheran Blood Group Glycoprotein
J. Biol. Chem.,
June 22, 2001;
276(26):
23757 - 23762.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
