Figure 1

Effects of MK2 inhibitors of the growth and morphology of WS fibroblasts. (a) Structures of the MK2 inhibitors. (b) F-actin stress fibre phenotype of primary AG05229 cells grown in the presence of 5.0 μM inhibitor 2 (a similar phenotype is seen at 2.5 μM). Bar = 100 μm. (c) Titration inhibition of MK2 profile by MK2.III as measured by HSP27 phosphorylation ELISA. (d, e) Growth of primary WS AG05229 and NDF AG04552 cells in the presence of MK2.III and SB203580 in population doublings (PDs) versus days. (f) Histogram illustrating the percentage increase in replicative capacity of WS fibroblasts compared to NDFs for the various treatments with DMSO = 100% lifespan. This data is an average of two strains for both WS (AG05229 and AG03141) and NDFs (AG04552 and AG13152) as illustrated by the error bars thus showing reproduciblity. The lifespan is calculated by taking into account the PDs already attained by the cells prior to arrival from the Coriell cell repository, e.g., for AG05229 the lifespan for 5.0 μM MK2.III treatment is (26.5 PD – 7 PD)/(20.5 PD – 7 PD) = 1.444 = 144.4%. (g) Effects of SB203580 or MK2.III on the cellular morphology and F-actin stress fibre phenotype of WS fibroblasts and NDFs. Bar = 100 μm; all panels same magnification.