Chemical modification of human growth hormone with N-acetylimidazole. Effect on binding capacity to lactogenic and somatogenic receptors.
The effect of acetylation of tyrosine residues on the binding capacity of human growth hormone (hGH) to rat liver lactogenic and somatogenic receptors was studied. When 3.7 tyrosine and 4.8 lysine residues were acetylated with N-acetylimidazole, both the in vivo and the in vitro capacities of hGH to compete with 125I-labeled bovine growth hormone for somatogenic binding sites greatly decreased. Acetylation also affected the in vitro binding capacity to lactogenic sites. Most of the somatogenic binding activity was recovered by hydroxylamine treatment, which removes O-acetyl groups from tyrosine residues but not N-acetyl groups from lysine residues. The same treatment partially restored lactogenic binding capacity. The reactivity of hGH tyrosine residues to N-acetylimidazole, together with previous evidence, suggests that: (a) Tyrosine residues 160 and 164, when acetylated, are likely to be responsible for the low binding activity of acetylated hGH. (b) Tyrosine 160 may play a significant role in hGH interaction with lactogenic receptors.
Kaliman
P
P
Institute of Biochemistry and Biophysic Chemistry (UBA-CONICET) Faculty of Pharmacy and Biochemistry, Buenos Aires, Argentina.
Ermácora
M R
MR
Nowicki
C
C
Wolfenstein-Todel
C
C
Santomé
J A
JA
D000107:Acetylation; D000818:Animals; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D005260:Female; D013006:Growth Hormone / Q000737:chemistry / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry*; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018000:Receptors, Peptide; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014443:Tyrosine / Q000737:chemistry*
D007093:Imidazoles; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011986:Receptors, Somatotropin; C028202:placental lactogen receptor; D014443:Tyrosine; D013006:Growth Hormone; C012160:N-acetylimidazole