CD98hc (SLC3A2) interaction with the integrin β subunit cytoplasmic domain mediates adhesive signaling

Gerald W. Prager, Chloé C. Féral, Chungho Kim, Jaewon Han, Mark H. Ginsberg

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In mammals, β1 integrin adhesion receptors generate signals that mediate cell spreading, migration, proliferation, and survival. CD98, a heterodimeric transmembrane protein, physically associates with certain integrin β subunit cytoplasmic domains (tails) via its heavy chain, CD98hc (SLC3A2), and loss of CD98hc impairs integrin signaling. Here we have used the lack of CD98hc interaction with the Drosophila integrin βPS tail for a homology scanning analysis that implicated the C-terminal 8 residues of β3 (Thr755-Thr802) in CD98hc binding. We then identified point mutations in the β3 C terminus (T755K and T758M) that abolish CD98hc association and a double mutation in the corresponding residues in the βPS tail (K839T,M842T), which resulted in gain of CD98hc interaction. Furthermore, the loss of function β3(T755K) mutation or the gain of function β3/βPS(K839T,M842T) led to a loss or gain of integrin-mediated cell spreading, respectively. Thus, we have identified critical integrin residues required for CD98hc interaction and in doing so have shown that CD98c interaction with the integrin β tail is required for its ability to mediate integrin signaling. These studies also provide new insights into how CD98hc may cooperate with other cytoplasmic domain binding proteins to modulate integrin functions and into the evolution of integrin signaling.

Original languageEnglish
Pages (from-to)24477-24484
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number33
DOIs
Publication statusPublished - 2007 Aug 17
Externally publishedYes

Fingerprint

Integrins
Adhesives
Tail
Mutation
Mammals
Point Mutation
Cell Movement
Carrier Proteins
Scanning

ASJC Scopus subject areas

  • Biochemistry

Cite this

CD98hc (SLC3A2) interaction with the integrin β subunit cytoplasmic domain mediates adhesive signaling. / Prager, Gerald W.; Féral, Chloé C.; Kim, Chungho; Han, Jaewon; Ginsberg, Mark H.

In: Journal of Biological Chemistry, Vol. 282, No. 33, 17.08.2007, p. 24477-24484.

Research output: Contribution to journalArticle

Prager, Gerald W. ; Féral, Chloé C. ; Kim, Chungho ; Han, Jaewon ; Ginsberg, Mark H. / CD98hc (SLC3A2) interaction with the integrin β subunit cytoplasmic domain mediates adhesive signaling. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 33. pp. 24477-24484.
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