%0 Journal Article
%T ¦Â1 integrins show specific association with CD98 protein in low density membranes
%A Tatiana V Kolesnikova
%A Brian A Mannion
%A Fedor Berditchevski
%A Martin E Hemler
%J BMC Biochemistry
%D 2001
%I BioMed Central
%R 10.1186/1471-2091-2-10
%X We demonstrate that CD98 constitutively and specifically associates with ¦Â1 integrins (¦Á2¦Â1,¦Á3¦Â1, ¦Á5¦Â1 and ¦Á6¦Â1), but minimally with ¦Á4¦Â1. Integrin-CD98 association was established by reciprocal immunoprecipitation experiments, and confirmed by CD98-induced clustering of ¦Á3¦Â1 but not ¦Á4¦Â1 on the surface of rhabdomyosarcoma cells. Integrin-CD98 association is independent of the ¦Á subunit cytoplasmic tail, is maintained in ¦Á3¦Â1 ligand-interaction deficient mutants, and is not inhibited by EDTA. Within the CD98 heavy chain, a C109S mutation (but not a C330S mutation) caused a loss of ¦Â1 integrin association. The same C109S mutation also caused a loss of CD98 light chain association. Importantly, CD98 associated selectively with ¦Â1 integrins present in low density "light membrane" fractions on a sucrose gradient. CD98 was not present in dense fractions that contained the majority of ¦Â1 integrins. Notably, the C109S mutant of CD98, that did not associate with ¦Â1 integrins, showed also a reduced localization into light membrane fractions.We demonstrate that CD98 association with ¦Â1 integrins is specific, occurs in the context of low density membranes, and may require the CD98 light chain.The CD98 (4F2, FRP-1) molecule, a cell surface disulfide-linked heterodimer, was originally described as a T cell activation antigen [1], and later was shown to provide a co-stimulatory signal for CD3-mediated T-cell activation [2], independent of CD28/CD80/CD86 interaction [3]. In other studies, triggering of human monocyte CD98 could suppress T cell proliferation [4], or promote homotypic cell aggregation of monocytes [5]. Also, CD98 may be a target antigen for natural killer cells [6], may mediate fusion of blood monocytes leading to osteoclast formation [7,8], and may modulate hematopoietic cell survival and differentiation [9].The CD98 molecule is also widely expressed on rapidly growing non-hematopoietic cells, where it may modulate oncogenic transformation [10,11], metal ion transp
%U http://www.biomedcentral.com/1471-2091/2/10