IB1, a JIP-1-related nuclear protein present in insulin-secreting cells.
JIP-1 is a cytoplasmic inhibitor of the c-Jun amino-terminal kinase activated pathway recently cloned from a mouse brain cDNA library. We report herein the expression cloning of a rat cDNA encoding a JIP-1-related nuclear protein from a pancreatic beta-cell cDNA library that we named IB1 for Islet-Brain 1. IB1 was isolated by its ability to bind to GTII, a cis-regulatory element of the GLUT2 promoter. The IB1 cDNA encodes a 714-amino acid protein, which differs from JIP-1 by the insertion of 47 amino acids in the carboxyl-terminal part of the protein. The remaining 667 amino acids are 97% identical to JIP-1. The 47-amino acid insertion contains a truncated phosphotyrosine interaction domain and a putative helix-loop-helix motif. Recombinant IB1 (amino acids 1-714 and 280-714) was shown to bind in vitro to GTII. Functionally IB1 transactivated the GLUT2 gene. IB1 was localized within the cytoplasm and the nucleus of insulin-secreting cells or COS-7 cells transfected with an expression vector encoding IB1. Using a heterologous GAL4 system, we localized an activation domain of IB1 within the first 280 amino acids of the protein. These data demonstrate that IB1 is a DNA-binding protein related to JIP-1, which is highly expressed in pancreatic beta-cells where it functions as a transactivator of the GLUT2 gene.
Bonny
C
C
Department of Internal Medicine B, University Hospital, Lausanne, Switzerland.
Nicod
P
P
Waeber
G
G
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004251:DNA Transposable Elements; D018076:DNA, Complementary / Q000737:chemistry; D015723:Gene Library; D051273:Glucose Transporter Type 2; D018257:Helix-Loop-Helix Motifs; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D012984:Software; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D051273:Glucose Transporter Type 2; D007328:Insulin; C490665:Mapk8ip protein, mouse; C110528:Mapk8ip1 protein, rat; D009004:Monosaccharide Transport Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D019000:Phosphotyrosine; D004247:DNA