Phosphorylation of PIP5K by Akt: a regulatory role for focal adhesion dynamics

조회수 : 246 등록일 : 2016.04.27 08:28

일시 : 2016.04.27 17:00
소속 : 아주대학교 의대 대학원 의생명과학과
발표자 : 이상윤
장소 : R404
The type I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family members and their lipid product, phosphatidylinositol 4,5-bisphosphate (PIP2) are important regulators of actin cytoskeleton. PIP5Kγ 90 kDa (PIP5Kγ90), an isoform of PIP5K, localizes to focal adhesions (FAs) and is activated via its interaction with the cytoskeletal protein, talin. Currently, regulatory signaling pathways of talin–PIP5Kγ90 interaction related to FA dynamics and cell motility are not well understood. Considering the presence of Akt consensus motifs in PIP5Kγ90, we examined a potential link of Akt activation to talin–PIP5Kγ90 interaction. We found that Akt phosphorylated PIP5Kγ90 specifically at serine 555 (S555) in vitro and in epidermal growth factor (EGF)-treated cells phosphoinositide 3-kinase-dependently. EGF treatment suppressed talin–PIP5Kγ90 interaction and PIP2 levels. Similarly, a phosphomimetic mutant (S555D), but not non-phosphorylatable mutant (S555A), of PIP5Kγ90 had reduced talin binding affinity, lowered PIP2 levels, andwas dislocated fromFAs. The S555Dmutant also caused decreases in actin stress fibers and vinculin-positive FAs.Moreover, assembly and disassembly of FAs were enhanced by S555D expression and EGF-induced cell migration was relatively low in S555A-expressing cells compared to wild-type-expressing cells. PIP5Kγ87, a PIP5Kγ splice variant lacking the talin binding motif, was phosphorylated by Akt, which, however, hardly affected PIP2 levels. Taken together, our results suggested that Akt-mediated PIP5Kγ90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility.
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