The granulin/epithelin precursor abrogates the requirement for the insulin-like growth factor 1 receptor for growth in vitro.
3T3 cells null for the type 1 insulin-like growth factor receptor are refractory to stimulation by a variety of purified growth factors that are known to be required for the stimulation of other 3T3 cells. However, these cells, known as R- cells, grow in serum-supplemented medium and also in media conditioned by certain cell lines. We report here the purification of a growth factor that stimulates DNA synthesis (and growth) of R- cells. The growth factor, purified to homogeneity by SDS-polyacrylamide gel electrophoresis, was identified as the granulin/epithelin precursor by an accurate determination of the masses of endoproteinase Lys-C peptides using matrix-assisted laser desorption ionization mass spectrometry, followed by a data base search. The granulin/epithelin precursor is a little known growth factor, secreted by a variety of epithelial and hemopoietic cells. It is at present the only purified growth factor that can stimulate the growth of mouse embryo fibroblasts null for the type 1 insulin-like growth factor receptor.
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
S Q
SQ
Xu
D
D
Tang
S
S
Chamberlain
G
G
Pronk
F R
FR
Masiarz
S
S
Kaur
M
M
Prisco
T
T
Zanocco-Marani
R
R
Baserga
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D003470:Culture Media / Q000737:chemistry; D017077:Culture Media, Conditioned / Q000737:chemistry; D004261:DNA Replication / Q000187:drug effects; D019992:Databases as Topic; D004622:Embryo, Mammalian / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D000077153:Progranulins; D011498:Protein Precursors / Q000737:chemistry*; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014764:Viral Proteins / Q000502:physiology*
D003470:Culture Media; D017077:Culture Media, Conditioned; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D000077153:Progranulins; D011498:Protein Precursors; D014764:Viral Proteins; D017526:Receptor, IGF Type 1; D008666:Metalloendopeptidases; C039830:peptidyl-Lys metalloendopeptidase