Hormonal and developmental regulation of glycosylated α2u-globulin synthesis

Haars, Laura; Pitot, Henry C.

doi:10.1016/0003-9861(80)90545-7

Cited by 10 publications

(4 citation statements)

References 29 publications

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“…It has been reported that the only amino sugar in the glycosylated form of a2u-globulin is N-acetylglucosamine (11,12).…”

Section: And Discussionmentioning

confidence: 99%

“…5, black dot). A single base change at this site in another expressed a2u-globulin gene would explain the existence of both glycosylated and nonglycosylated forms of this protein (11,12). An analysis of this region of the amino acid chain by the predictive scheme of Chou and Fasman (44) indicates that this asparagine residue is contained in a sequence (residues 34-37) that exhibits a strong potential to exist in 8-turn conformation (45).…”

Section: And Discussionmentioning

confidence: 99%

“…This regulation in vivo has been shown to occur via modulation of the rate of synthesis of hepatic a2u-globulin mRNA (5, 10). The existence of both glycosylated and nonglycosylated forms of a2,-globulin has been reported (11,12), as well as induction of the glycosylated form by glucocorticoids (13,14). a2u-Globulin is first synthesized as the 21,000-dalton precursor pro-a2u-globulin, which is then processed to the mature form of the protein (15).…”

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confidence: 99%

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Cloning and sequence of several alpha 2u-globulin cDNAs.

Unterman¹,

Lynch²,

Nakhasi³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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We describe a simple cloning procedure for a%.-globulin that requires neither enrichment of mRNA for cloning nor purification of a specific probe for screening recombinant colonies. Total adult male liver poly(A)+RNA was used as template for cloning, and the subsequent recombinant colonies were screened by comparing hybridization to radioactive cDNA probes prepared from hepatic male and female mRNA, respectively. Almost all of the selected "male-specific" clones were later shown to contain a2,-globulin sequences. This cloned au-globulin cDNA has been shown to specifically hybridize to male rat liver RNA, which, when isolated and translated in vitro, codes for a 21,000-dalton protein (pro-a2u-globulin) immunologically identical to auglobulin. When translation occurs in the presence of pancreatic microsomes this in vitro synthesized pro-a2u-globulin is processed to the 19,000-dalton mature form of a2u-globulin. The nucleotide sequence of the a2u-globulin cDNA has been determined, thus elucidating the complete amino acid sequence of a2.-globulin and most of the hydrophobic "leader" sequence of pro-a2u-globulin.The amino acid sequence deduced from the cDNA is in agreement with the partial sequence that we previously determined by sequential Edman degradation ofthe purified-protein. a2u-Globulin cDNA clones contain within the.3'-untranslated region one or both of the two putative polyadenylylation/transcription termination sites (A-A-T-A-A-A and A-A-T-T-A-A-A). Either of these can be used, generating a2u-globulin mRNA species of two lengths. A codon usage analysis of the cDNA showed that, although all six leucine codons are used for the 14 leucine residues in mature auglobulin, the seven leucines in the partial leader sequence reported are all encoded by the same codon, CTG. The primary amino acid sequence contains a unique Asn-Gly-Ser sequence, likely to be in (-turn conformation, as the probable site of glycosylation for this glycoprotein.ac2u-Globulin is synthesized in the liver of normal adult male rats, secreted into the bloodstream, and excreted in the urine (1), and represents ':'1% of total hepatic protein synthesis (2). Female liver, male kidney, and several hepatomas do not synthesize a2u-globulin and have no detectable a2,,-globulin mRNA sequences (2-4). The biosynthesis of a2u-globulin is also under complex multihormonal control: androgens, glucocorticoids, thyroid hormone, insulin, and growth hormone stimulate and estrogens repress its synthesis (5-9). This regulation in vivo has been shown to occur via modulation of the rate of synthesis of hepatic a2u-globulin mRNA (5, 10). The existence of both glycosylated and nonglycosylated forms of a2,-globulin has been reported (11,12), as well as induction of the glycosylated form by glucocorticoids (13,14). a2u-Globulin is first synthesized as the 21,000-dalton precursor pro-a2u-globulin, which is then processed to the mature form of the protein (15).As part of our ongoing research into the regulation of a2u-globulin synthesis, we have cloned the cDNA ...

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“…It has been reported that the only amino sugar in the glycosylated form of a2u-globulin is N-acetylglucosamine (11,12).…”

Section: And Discussionmentioning

confidence: 99%

Section: And Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Cloning and sequence of several alpha 2u-globulin cDNAs.

Unterman¹,

Lynch²,

Nakhasi³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…Zielonka et al have also shown that testosterone increases the skin secretion of Eel d 1 [21]. These hormonal effects may be tissue-specific; the salivary production of allergenie rat and mouse proteins for example, is less infiuenced by testosterone levels [22][23][24]. This differential regulation may explain in part, why female animals are still capable of secreting significant levels of allergen [20,25].…”

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confidence: 98%