Phosphoprotein B-50: localization of proteolytic sites for S. aureus V8 protease using truncated cRNAs for cell-free translation

J Mol Neurosci. 1991;3(2):85-93. doi: 10.1007/BF02885529.

Abstract

B-50 (= GAP-43, F1, and P-57 or neuromodulin) is a nervous tissue-specific, growth-associated protein, localized in the presynaptic membrane. Phosphorylation by protein kinase C at Ser41 appears to play a role in B-50/calmodulin interaction and neurotransmitter release. Previous studies have shown that digestion of the phosphorylated protein with S. aureus V8 protease (SAP) resulted consecutively in 28- and 15-kDa phospho fragments, the latter containing all incorporated phosphate. These proteolytic products of digestion with SAP have frequently been used to identify B-50 in various systems. Therefore we were interested to find out the location of these fragments in the rat B-50 molecule. For this purpose, the rat cDNA for B-50 was used to generate full-length and truncated cRNAs for cell-free translation. B-50 and B-50 peptides were either N-terminally labeled with [35S]methionine (residues 1 and 5) as a tracer, or they were phosphorylated in vitro by protein kinase C. SAP digestion of the immunoprecipitated, 35S-labeled translation products produced similar 28- and 15-kDa fragments as were obtained from 32P-labeled B-50, indicating that these fragments are N-terminal. Relative mobilities of the N-terminal B-50 fragments of known length were used as internal standards for the calculation of the length of SAP and phospho fragments. Comparing the 35S- and 32P-labeled products, four SAP sites at Glu12, Glu28, Glu65, and Glu132 could be deduced. The latter two sites are in accordance with sequence data of C-terminal fragments from the literature. All available data could be fitted into one scheme.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calmodulin-Binding Proteins / genetics
  • Calmodulin-Binding Proteins / metabolism*
  • Cell-Free System
  • DNA / genetics
  • DNA Restriction Enzymes / metabolism
  • GAP-43 Protein
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Peptide Fragments / metabolism
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Biosynthesis
  • RNA / metabolism
  • RNA, Complementary
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Serine Endopeptidases / metabolism*

Substances

  • Calmodulin-Binding Proteins
  • GAP-43 Protein
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Phosphoproteins
  • RNA, Complementary
  • Recombinant Fusion Proteins
  • RNA
  • DNA
  • DNA Restriction Enzymes
  • Serine Endopeptidases
  • glutamyl endopeptidase