Ser13‐phosphorylated PYY from porcine intestine with a potent biological activity

FEBS Letters

Jonsson, Andreas P.³  Eriste, Elo³  Chen, Zheng-wang³  Bergman, Tomas³  Efendic, Suad²  Lovenberg, Timothy W.¹  Nepomuceno, Diane¹  Norberg, Åke³  Jörnvall, Hans³  Sillard, Rannar³ 

[1]R.W. Johnson Pharmaceutical Research Institute, San Diego, CA 92121, USA

[2]Department of Molecular Medicine, Karolinska Hospital, SE-171 76 Stockholm, Sweden

[3]Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden

关键词: Peptide hormone phosphorylation;    Casein kinase;    cAMP production;    Receptor binding;    Mass spectrometry;   

DOI  :  10.1016/S0014-5793(01)02234-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have isolated a posttranslationally modified form of peptide YY (PYY) from porcine intestine and shown by MALDI-TOF and electrospray tandem mass spectrometry that it is phosphorylated at Ser¹³. Phospho-PYY exhibits high affinity for binding to neuropeptide Y (NPY) receptors Y1, Y2 and Y5. The IC₅₀ values with the Y1, Y2, and Y5 receptor subtypes were for NPY 2.4, 3.1, and 3.3 nM, for PYY 2.3, 0.94, and 3.2 nM, and for phospho-PYY 4.6, 2.2, and 5.5 nM, respectively. Phospho-PYY potently inhibits forskolin-stimulated cAMP accumulation in SK-N-MC cells with an IC₅₀ value of 0.5 nM compared to 0.15 nM for non-phosphorylated PYY. The finding of phosphorylation of PYY is unusual among hormonal peptides, and emphasizes the importance of direct protein analysis of gene products.

【 授权许可】

Unknown