Molecular cloning of the 18-kDa growth-associated protein of developing brain

J Biol Chem. 1990 Oct 5;265(28):16721-4.


An 18-kDa protein (designated herein as the heparin-binding growth-associated molecule, HB-GAM), the expression of which in rat brain correlates to the rapid postnatal developmental phase, was previously isolated and suggested to have a role in the maturation and growth of brain (Rauvala, H. (1989) EMBO J. 8, 2933-2941). A protein with a similar molecular mass, similar heparin-binding properties, and the same N-terminal sequence was more recently also isolated as a mitogen for NIH 3T3 cells (Milner, P. G., Li, Y.-T., Hoffman, R. M., Kodner, C. M., Siegel, N. R., and Deuel, T. F. (1989) Biochem. Biophys. Res. Commun. 165, 1096-1103). This study reports the cloning and sequencing of the cDNA that encodes HB-GAM. The sequence that precedes the structure of the mature molecule has the characteristics of a signal sequence found in secretory proteins. The sequence of HB-GAM is a novel structure that contains 136 amino acid residues. The sequence is very rich in cationic amino acids (24% of the residues); lysine cluster sequences are found in the N-terminal and C-terminal ends of the structure. Cysteine is also abundant in the sequence (7% of the residues). The only homologous sequence found in computer searches is the retinoic acid-induced differentiation factor. The mRNA of HB-GAM detected by the cloned cDNA shows the same kind of developmental regulation as the protein; the mRNA is strongly expressed during the early postnatal growth phase of rat brain as compared with embryonic or adult tissue.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / growth & development*
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Cytokines / genetics*
  • Gene Expression
  • Gene Library
  • Growth Substances / genetics*
  • Molecular Sequence Data
  • Molecular Weight
  • Oligonucleotide Probes
  • Organ Specificity
  • Phosphatidylinositol Phosphates*
  • Phosphatidylinositols / blood*
  • Protein Conformation
  • RNA, Messenger / genetics
  • Rats
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid


  • Carrier Proteins
  • Cytokines
  • Growth Substances
  • Oligonucleotide Probes
  • Phosphatidylinositol Phosphates
  • Phosphatidylinositols
  • RNA, Messenger
  • phosphatidylinositol 3,4,5-triphosphate
  • pleiotrophin

Associated data

  • GENBANK/J05657
  • GENBANK/M55601