DIFFERENTIAL-EFFECTS OF THE INTEGRINS ALPHA-9-BETA-1, ALPHA-V-BETA-3,AND ALPHA-V-BETA-6 ON CELL PROLIFERATIVE RESPONSES TO TENASCIN - ROLES OF THE BETA-SUBUNIT EXTRACELLULAR AND CYTOPLASMIC DOMAINS
Y. Yokosaki et al., DIFFERENTIAL-EFFECTS OF THE INTEGRINS ALPHA-9-BETA-1, ALPHA-V-BETA-3,AND ALPHA-V-BETA-6 ON CELL PROLIFERATIVE RESPONSES TO TENASCIN - ROLES OF THE BETA-SUBUNIT EXTRACELLULAR AND CYTOPLASMIC DOMAINS, The Journal of biological chemistry, 271(39), 1996, pp. 24144-24150
Members of the integrin family manifest considerable overlap in ligand
specificity, and many cells have the capacity to express multiple int
egrin receptors for the same ligand. For example, at least 5 different
integrins recognize tenascin as a ligand, and 4 of these bind to the
same region of the protein, the third fibronectin type III repeat (TNf
n3). We utilized colon carcinoma cells (SW480) that do not normally at
tach to TNfn3 to examine the possibility that ligation of different in
tegrin receptors for this ligand would induce different effects on cel
l behavior and intracellular signaling. Heterologous expression of the
tenascin receptors alpha v beta 3 and alpha 9 beta 1 produced compara
ble effects on cell adhesion and spreading on TNfn3, but alpha v beta
3-transfectants proliferated considerably better on each concentration
examined, alpha v beta 6-transfectants attached (although less avidly
), but completely failed to spread or proliferate. Expression of a chi
meric beta subunit composed of the beta 3 extracellular domain fused t
o the beta 6 transmembrane and cytoplasmic domains resulted in adhesio
n and spreading similar to that seen with beta 3-transfectants, but co
nsiderably less proliferation. When the same cell lines were plated on
fibronectin, alpha v beta 6-transfectants spread and proliferated as
well as cells transfected with the chimeric beta 3/beta 6 subunit, but
, again, neither cell line proliferated as well as cells expressing al
pha v beta 3. Cell proliferation was always associated with spreading
and with phosphorylation of the focal adhesion kinase, paxillin, and t
he mitogen-activated kinase, Erk2, but cell attachment in the absence
of spreading or proliferation was not associated with phosphorylation
of any of these proteins. These data suggest that different integrin r
eceptors for a single ligand can produce markedly different effects on
cell proliferation, and that both the extracellular and cyto plasmic
domains of integrin beta subunits contribute to these differences.