Altered proteolytic cleavage of human growth hormone as a result of deamidation.

U. J. Lewis, R. N. Singh, Lynda Bonewald, B. K. Seavey

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

The major desamido form of human growth hormone (hGH) results from deamidation of asparagine 152. Peptide mapping and amino acid sequencing were used in the identification. This desamido form (hGHAsp152) could be produced by incubation of the undeamidated hormone in an alkaline medium. Another minor deamidated form which contained glutamic acid at 137 (hGHGlu137) also was identified in preparations of hGH. This form was not produced by alkaline treatment of hGH. Limited hydrolysis of hGH with subtilisin produced two cleaved forms, one with cleavages at positions 139 and 149 and another with cleavages at 139 and 146. hGHAsp152 underwent only one type of modification, cleavage at positions 139 and 146. Hydrolysis of hGHGlu137 resulted in cleavages in the region of 139 to 149 identical with those noted with hGH, but in addition, proteolysis had occurred in the region of 95 to 127, an area where hGH was not attacked by subtilisin. That Glu at 137 modified cleavage points was also indicated by the greater resistance of hGHGlu137 to hydrolysis by subtilisin as compared to hGH. The results demonstrate that deamidation can alter points of proteolytic cleavage. If proteolytic processing of hGH is found to be of physiologic significance, deamidation may be a way of directing specific cleavages.

Original languageEnglish (US)
Pages (from-to)11645-11650
Number of pages6
JournalJournal of Biological Chemistry
Volume256
Issue number22
StatePublished - Nov 25 1981
Externally publishedYes

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Human Growth Hormone
Subtilisin
Hydrolysis
Proteolysis
Peptide Mapping
Asparagine
Protein Sequence Analysis
Glutamic Acid
Hormones
Amino Acids
Peptides
Processing

ASJC Scopus subject areas

  • Biochemistry

Cite this

Altered proteolytic cleavage of human growth hormone as a result of deamidation. / Lewis, U. J.; Singh, R. N.; Bonewald, Lynda; Seavey, B. K.

In: Journal of Biological Chemistry, Vol. 256, No. 22, 25.11.1981, p. 11645-11650.

Research output: Contribution to journalArticle

Lewis, U. J. ; Singh, R. N. ; Bonewald, Lynda ; Seavey, B. K. / Altered proteolytic cleavage of human growth hormone as a result of deamidation. In: Journal of Biological Chemistry. 1981 ; Vol. 256, No. 22. pp. 11645-11650.
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