Structural and physiologic characterization of the mid-region secretory species of parathyroid hormone-related protein.
Parathyroid hormone-related protein (PTHrP) is initially translated as a preprohormone which is posttranslationally processed to yield a family of mature secretory forms. Most attention has focused on the amino-terminal portion of the molecule which is homologous to parathyroid hormone. It is clear, however, that a mid-region species of PTHrP is posttranslationally cleaved from the highly conserved mid-region of PTHrP, and that the amino terminus of this peptide is Ala38. The purposes of the current study were three: 1) to confirm that Arg37 immediately preceding Ala38 serves as a posttranslational processing site in the PTHrP precursor, 2) to determine the carboxyl terminus of the mid-region secretory species of PTHrP, and 3) to synthesize this authentic mid-region secretory form of PTHrP and determine whether it is biologically active. The results indicate that: 1) Arg37 is indeed a processing site in the PTHrP precursor; 2) three distinct mid-region PTHrP species are generated by posttranslational processing, PTHrP(38-94)amide, PTHrP(38-95), and most likely, PTHrP(38-101); and 3) synthetic mid-region PTHrP(38-94)amide is active in four different biological systems. These studies confirm the finding that PTHrP is a prohormone. More importantly, they define a novel, biologically active highly conserved mid-region secretory form of PTHrP.
Wu
T L
TL
Division of Endocrinology, Connecticut Veterans Affairs Medical Center, West Haven, Connecticut 06516, USA.
Vasavada
R C
RC
Yang
K
K
Massfelder
T
T
Ganz
M
M
Abbas
S K
SK
Care
A D
AD
Stewart
A F
AF
D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D010449:Peptide Mapping; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014357:Trypsin / Q000737:chemistry; D014407:Tumor Cells, Cultured
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D001120:Arginine; D014357:Trypsin