Open AccessIdentification of pp120, an endogenous substrate for the hepatocyte insulin receptor tyrosine kinase, as an integral membrane glycoprotein of the bile canalicular domain.
Author(s) -
Ronald N. Margolis,
Simeon I. Taylor,
Daniela Seminara,
Ann L. Hubbard
Publication year - 1988
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.85.19.7256
Subject(s) - biochemistry , irs2 , tyrosine kinase , insulin receptor , ror1 , receptor tyrosine kinase , insulin receptor substrate , biology , insulin , receptor , platelet derived growth factor receptor , endocrinology , insulin resistance , growth factor
An endogenous membrane-bound substrate of the insulin receptor beta-subunit tyrosine kinase in liver, pp120, has been identified as HA4, a 110-kDa membrane glycoprotein localized primarily to the bile canalicular domain of the hepatocyte. HA4 has been implicated in bile salt transport and cell adhesion. Monoclonal antibodies to HA4 were used to identify it as a substrate of the insulin receptor kinase. Anti-pp120 and anti-HA4 were found to cross-react, and phosphopeptide maps for each of the corresponding antigens were identical. The identification of pp120 as HA4 serves to link insulin action through the receptor tyrosine kinase activity to bile metabolism and raises questions pertaining to the intracellular site(s) of action of the insulin receptor.