title: Aberrant postendocytotic fate of a 34-kDa molecular mass growth factor from human trophoblasts.
abstract: A 34-kDa growth factor expressed by trophoblasts and certain carcinomas binds to target fibroblastic cells through specific high-affinity receptors. Here we report studies on the cellular routing behavior of the receptor-bound 34-kDa protein. Internalization was visualized by using lissamine rhodamine-conjugated 34-kDa protein and was quantified by analyzing the acid dissociability of cell-bound radioiodinated protein after incubation at 37 degrees C. The protein was found to be rapidly internalized in a temperature-sensitive manner. However, in contrast with other protein ligands, the 34-kDa protein was not rapidly degraded. The extent of ligand degradation was small as quantified by gel filtration analysis. Studies on the receptor showed that there was an atypical up-regulation, i.e., increase in surface receptors in response to ligand binding at 37 degrees C. The up-regulation was partially blocked by cycloheximide, an inhibitor of protein biosynthesis, but not by known inhibitors of receptor recycling such as monensin, chloroquine, and methylamine, suggesting that enhanced receptor biosynthesis may be responsible for the process. These studies indicate that the cellular routing and receptor regulatory characteristics of the internalized 34-kDa growth factor are different from those of most growth factor ligands and imply the involvement of receptor up-regulation in signal transduction.
authors.affiliation: Department of Biochemistry, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: M
authors.initials: M
authors.lastname: Das
authors.forename: S S
authors.initials: SS
authors.lastname: Chauhan
authors.forename: V S
authors.initials: VS
authors.lastname: Mishra
authors.forename: J M
authors.initials: JM
authors.lastname: Sanger
authors.forename: J W
authors.initials: JW
authors.lastname: Sanger
authors.forename: S
authors.initials: S
authors.lastname: Roy-Choudhury
mesh_terms: D002478:Cells, Cultured; D004705:Endocytosis; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D011975:Receptors, Mitogen / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D006133:Growth Substances; D011975:Receptors, Mitogen