Open AccessIdentification of Stat 5B as a Substrate of the Insulin Receptor
Author(s) -
SawkaVerhelle Dominique,
Filloux Chantal,
TartareDeckert Sophie,
Mothe Isabelle,
Obberghen Emmanuel
Publication year - 1997
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1997.0411a.x
Subject(s) - irs2 , insulin receptor , insulin receptor substrate , tropomyosin receptor kinase c , insulin like growth factor 1 receptor , ror1 , microbiology and biotechnology , grb10 , 5 ht5a receptor , receptor tyrosine kinase , biology , tropomyosin receptor kinase b , insulin , receptor , biochemistry , phosphorylation , platelet derived growth factor receptor , endocrinology , insulin resistance , growth factor , neurotrophic factors
We have screened a human placenta library using the yeast two‐hybrid system to identify proteins that interact with the cytoplasmic domain of the insulin receptor. Doing so, we trapped a cDNA clone which encodes the Stat 5B region comprising amino acids 469 to 786. We show that interaction between Stat 5B and the receptor requires a functional insulin‐receptor Kinase, Tyr960 of insulin receptor is implicated in the interaction with Stat 5B, whereas asparagine and proline forming the NPEY960‐motif are not, and Stat 5B mutated at Thr684, a potential phosphorylation site of mitogen‐activated protein Kinase, loses its ability to interact with the insulin receptor. Further, we found that insulin promotes rapid tyrosine phosphorylation of endogenous Stat 5B in 293 EBNA cells overexpressing insulin receptor and in NHIR cells. Taken together, our finding suggest that Stat 5B corresponds to a substrate for the insulin‐receptor Kinase, and this widens the repertoire of insulin‐signaling pathways.