CD98 and intracellular adhesion molecule I regulate the activity of amino acid transporter LAT-2 in polarized intestinal epithelia.
We have previously shown that the heterodimer CD98/LAT-2 (LAT-2: amino acid transporter) is expressed in the basolateral membrane of intestinal epithelia and is associated with beta1 integrin (Merlin, D., Sitaraman, S., Liu, X., Easterburn, K., Sun, J., Kucharzik, T., Lewis, B., and Madara, J. L. (2001) J. Biol. Chem. 276, 39282-39289). In the present study we examined the interaction of CD98/LAT2 with intracellular adhesion molecule I (ICAM-1) and the potential of such interaction on the activation of intracellular signal in Caco2-BBE cell monolayers. ICAM-1 was found to be expressed to the basolateral domain and to selectively coimmunoprecipitate with CD98/LAT-2 in Caco2-BBE monolayers. Using antibodies as ligands to CD98 and ICAM-1, we demonstrate that the basolateral cross-linking of CD98 and ICAM-1 differentially affects the intrinsic activity of the LAT-2 transporter. Whereas CD98 ligation decreases the Km and Vm of the LAT-2 transporter, ICAM-1 ligation increases Km and Vm of the amino acid transporter LAT-2. In addition, basolateral cross-linking of CD98 or ICAM-1 induces threonine phosphorylation of an approximately 160-kDa supramolecular complex that is consistent with CD98/LAT-2-ICAM-1 complex. Together these findings demonstrate that (i). CD98/LAT-2 interacts with ICAM-1 in Caco2-BBE cell monolayers, and (ii). CD98 and ICAM-1 ligands generate intracellular signals that regulate the amino acids transporter (LAT-2) activity. Our data provide a novel mechanism by which events such as adhesion may be integrated by amino acid transport activity resulting from the direct interaction of cell surface molecules such as CD98 and ICAM-1.
Liu
Xia
X
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Charrier
Laetitia
L
Gewirtz
Andrew
A
Sitaraman
Shanthi
S
Merlin
Didier
D
D027182:Amino Acid Transport System y+; D001692:Biological Transport; D016764:Cell Polarity; D027301:Fusion Regulatory Protein 1, Light Chains / Q000378:metabolism*; D027261:Fusion Regulatory Protein-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism* / Q000502:physiology; D007413:Intestinal Mucosa / Q000166:cytology*; D007700:Kinetics; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D027182:Amino Acid Transport System y+; D027301:Fusion Regulatory Protein 1, Light Chains; D027261:Fusion Regulatory Protein-1; C420646:SLC7A8 protein, human; D018799:Intercellular Adhesion Molecule-1