CD44-mediated Akt activation is dependent on HAS2/HA. A–C,
Immunoblot analysis of pAkt levels showing that knockdown of HAS2
(A), treatment with HAS2 inhibitor 4-Mu (0.4 mmol/L;
B), or treatment with HAase (35 μg/mL; C)
abolished Akt activation in CD44s-overexpressing Mes10A cells. Cells were
stimulated with insulin 10 μg/mL for 30 minutes. D,
Immunoblot analysis showing that addition of CD44 antibodies abolishes
CD44s-promoted Akt activation in CD44s-overexpressing Mes10A cells. BD clone 515
and IM7 antibodies were added at 1 μg/mL concentration in starvation
media overnight. Cells were then washed with PBS and stimulated with insulin (10
μg/mL; 30 minutes). E, Immunoblot analysis showing that the
CD44 antibody IM7 blocks Akt activation in LM2 cells. LM2 cells were starved
overnight and then treated with IM7 antibody (10 μg/mL) for 3 hours,
followed by insulin stimulation (10 μg/mL; 30 minutes). F,
qRT-PCR analysis of HAS2 in control, CD44s-overexpressing, and HA-depleted
CD44s-overexpressing Mes10A cells. Treatment of CD44s-overexpressing Mes10A
cells with HAase (90 μg/mL) for 8 hours reduced CD44s-mediated HAS2
transcription. Error bars, SD; n = 3. *,
P < 0.05; ***,
P < 0.001.