title: Distinct domains of CD98hc regulate integrins and amino acid transport.
abstract: CD98 is a cell surface heterodimer formed by the covalent linkage of CD98 heavy chain (CD98hc) with several different light chains to form amino acid transporters. CD98hc also binds specifically to the integrin beta(1A) cytoplasmic domain and regulates integrin function. In this study, we examined the relationship between the ability of CD98hc to stimulate amino acid transport and to affect integrin function. By constructing chimeras with CD98hc and a type II transmembrane protein (CD69), we found that the cytoplasmic and transmembrane domains of CD98hc are required for its effects on integrin function, while the extracellular domain is required for stimulation of isoleucine transport. Consequently, the capacity to promote amino acid transport is not required for CD98hc's effect on integrin function. Furthermore, a mutant of CD98hc that lacks its integrin binding site can still promote increased isoleucine transport. Thus, these two functions of CD98hc are separable and require distinct domains of the protein.
authors: Department of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037 , USA.
authors: C A
authors: CA
authors: Fenczik
authors: R
authors: R
authors: Zent
authors: M
authors: M
authors: Dellos
authors: D A
authors: DA
authors: Calderwood
authors: J
authors: J
authors: Satriano
authors: C
authors: C
authors: Kelly
authors: M H
authors: MH
authors: Ginsberg
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D027261:Fusion Regulatory Protein-1; D016023:Integrins / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D016023:Integrins