Molecular cloning of the 18-kDa growth-associated protein of developing brain.
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.
Merenmies
J
J
Department of Medical Chemistry, University of Helsinki, Finland.
Rauvala
H
H
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression; D015723:Gene Library; D006133:Growth Substances / Q000235:genetics*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood*; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
D002352:Carrier Proteins; D016207:Cytokines; D006133:Growth Substances; D015345:Oligonucleotide Probes; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D012333:RNA, Messenger; C060974:phosphatidylinositol 3,4,5-triphosphate; C066845:pleiotrophin