Targeting of FAK Ser910 by Erk5 and PP1{delta} in non-stimulated and phorbol ester-stimulated cells

Emma Villa-Moruzzi (1)

1 Experimental Pathology

Ser910 of FAK was phosphorylated in fibroblasts treated with the phorbol ester TPA and dephosphorylated by Phosphatase1δ, as indicated by shRNA gene silencing. Ser910 was previously reported to be an Erk1/2 target in cells treated with phorbol esters. In contrast, various approaches, including the use of the MEK inhibitors UO126 and Cl-1040 to inhibit Erk1/2, pointed to the involvement of Erk5. This hypothesis was confirmed by: 1) shRNA Erk5 gene silencing, which resulted in complete pSer910 loss in non-stimulated and TPA-stimulated cells; 2) Erk5 direct phosphorylation of recombinant FAK; 3) Erk5 activation by TPA. TPA stimulation and Erk5 silencing in MDAMB 231 and 361 breast cancer cells indicated Ser910 targeting by Erk5 also in these cells. Given the proximity of S910 to the FAT regulatory domain of FAK, cell proliferation and morphology were investigated in FAK -/- cells expressing S910A FAK. Cell growth rate decreased and exposure to TPA induced peculiar morphological changes in cells expressing S910A, with respect to wild type FAK, suggesting a role for Ser910 in these processes. This investigation indicated, for the first time, the phosphorylation of Ser910 of FAK by Erk5 and its dephosphorylation by PP1δ, and suggested a role for Ser910 in the control of cell shape and proliferation.

Mots clés: Life Sciences

Emma Villa-Moruzzi. Targeting of FAK Ser910 by Erk5 and PP1{delta} in non-stimulated and phorbol ester-stimulated cells. Biochemical Journal, 2007, 408 (1), pp.7-18. ⟨10.1042/BJ20070058⟩. ⟨hal-00478735⟩