Identification of a cell retention signal in the B-chain of platelet-derived growth factor and in the long splice version of the A-chain

Cell Regul. 1991 Jul;2(7):503-12. doi: 10.1091/mbc.2.7.503.

Abstract

The B-chain homodimer of platelet-derived growth factor (PDGF) is only very inefficiently secreted and remains largely associated with the producer cell; in contrast, the dimer of the short, and most common, splice variant of the A-chain is secreted. To identify the structural background to the differences in the secretory pattern between the different isoforms of PDGF, a set of chimeric PDGF A/B cDNAs was generated and expressed in COS cells. Analyses of the biosynthesis and processing of the corresponding products led to the identification of a determinant for cell association in the carboxy-terminal third of the PDGF B-chain precursor. Introduction of stop codons at various positions in the carboxy-terminal prosequence of the PDGF B-chain localized this determinant to an 11-amino-acid-long region (amino acids 219-229). This region contains an 8-amino-acid-long basic sequence that is homologous to a sequence present in an alternatively spliced longer version of the PDGF A-chain. In contrast to the short splice variant, the long splice A-chain version, like the B-chain, was found to remain predominantly cell associated. Thus, we have identified a conserved sequence that inhibits the secretion of some of the PDGF isoforms. Our data also suggest that switching of splicing patterns can be a mechanism to regulate the formation of secreted or cell-associated forms of PDGF-AA and possibly other growth factors.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Compartmentation
  • Cell Line
  • Genetic Vectors
  • Molecular Sequence Data
  • Molecular Structure
  • Mutagenesis, Site-Directed
  • Platelet-Derived Growth Factor / chemistry*
  • Platelet-Derived Growth Factor / metabolism
  • Protein Sorting Signals / analysis*

Substances

  • Platelet-Derived Growth Factor
  • Protein Sorting Signals