Monkey growth hormone (GH) receptor gene expression - Evidence for two mechanisms for the generation of the GH binding protein

被引:52
作者
Martini, JF
Pezet, A
Guezennec, CY
Edery, M
PostelVinay, MC
Kelly, PA
机构
[1] FAC MED NECKER ENFANTS MALAD, INSERM, U344, F-75730 PARIS 15, FRANCE
[2] CERMA, DEPT PHYSIOL SYST, F-91228 BRETIGNY SUR ORGE, FRANCE
关键词
D O I
10.1074/jbc.272.30.18951
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The growth hormone receptor (GHR) cDNA was cloned from the liver of Rhesus macaque using polymerase chain reaction. As deduced from the nucleotide sequence, the mature GHR is a protein of 620 amino acids which presents 94.1% identity with the human receptor. The monkey GHR (mkGHR) expressed in 293 cells presented the expected specificity for a primate GHR and was able to transduce a transcriptional effect of GH. Human GH was able to activate tyrosine phosphorylation of both the tyrosine kinase JAK2 and the receptor in 293 cells co-transfected with mkGHR and JAK2 cDNAs. The GH binding protein (GHBP), the soluble short form of the GHR, was also present in monkey serum. Expression of the GHR cDNA in eucaryotic cells indicated that the GHBP can be produced by proteolytic cleavage of the membrane receptor. Northern blot analysis of GHR gene expression in different tissues allowed us to identify three different transcripts of 5.0 and 2.8 kilobase pairs and a smaller one of 1.7 kilobase pairs which could encode a GHBP. Rapid amplification of cDNA extremities (3'-RACE-polymerase chain reaction) was used to identify a cDNA encoding a protein in which the transmembrane and cytoplasmic domains of the receptor are substituted by a short sequence of 9 amino acids. This transcript was present in various tissues and could encode a GHBP as well, suggesting for the first time that two different mechanisms can coexist for the generation of the GHBP: proteolytic cleavage of the membrane receptor and a specific mRNA produced by alternative splicing.
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页码:18951 / 18958
页数:8
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