Identification of a receptor for reg (regenerating gene) protein, a pancreatic beta-cell regeneration factor.
Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem. 263, 2111-2114). Rat and human Reg gene products, Reg/REG proteins, have been demonstrated to stimulate islet beta-cell growth in vitro and in vivo and to ameliorate experimental diabetes. In the present study, we isolated a cDNA for the Reg protein receptor from a rat islet cDNA library. The cDNA encoded a cell surface 919-amino acid protein, and the cells into which the cDNA had been introduced bound Reg protein with high affinity. When the cDNA was introduced into RINm5F cells, a pancreatic beta-cell line that shows Reg-dependent growth, the transformants exhibited significant increases in the incorporation of 5'-bromo-2'-deoxyuridine as well as in the cell numbers in response to Reg protein. A homology search revealed that the cDNA is a homologue to a human multiple exostoses-like gene, the function of which has hitherto been unknown. These results strongly suggest that the receptor is encoded by the exostoses-like gene and mediates a growth signal of Reg protein for beta-cell regeneration.
Kobayashi
S
S
Department of Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan.
Akiyama
T
T
Nata
K
K
Abe
M
M
Tajima
M
M
Shervani
N J
NJ
Unno
M
M
Matsuno
S
S
Sasaki
H
H
Takasawa
S
S
Okamoto
H
H
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D051847:Lithostathine; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D051381:Rats; D011956:Receptors, Cell Surface / Q000302:isolation & purification*; D012038:Regeneration
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D051847:Lithostathine; D009419:Nerve Tissue Proteins; C497617:REG1A protein, human; D011956:Receptors, Cell Surface; C497616:Reg1a protein, rat