Hypertonic stress increases phosphatidylinositol 4,5-bisphosphate levels by activating PIP5KIβ

Masaya Yamamoto, Mark Z. Chen, Ying Jie Wang, Hui Qiao Sun, Yongjie Wei, Manuel Martinez, Helen L. Yin

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Hyperosmotic stress increases phosphoinositide levels, reorganizes the actin cytoskeleton, and induces multiple acute and adaptive physiological responses. Here we showed that phosphatidylinositol 4,5-bisphosphate (PIP 2) level increased rapidly in HeLa cells during hypertonic treatment. Depletion of the human type I phosphatidylinositol 4-phosphate 5-kinase β isoform (PIP5KIβ) by RNA interference impaired both the PIP2 and actin cytoskeletal responses. PIP5KIβ was recruited to membranes and was activated by hypertonic stress through Ser/Thr dephosphorylation. Calyculin A, a protein phosphatase 1 inhibitor, blocked the hypertonicity-induced PIP5KIβ dephosphorylation/activation as well as PIP2 increase in cells. Urea, which raises osmolarity without inducing cell shrinkage, did not promote dephosphorylation nor increase PIP2 levels. Disruption or stabilization of the actin cytoskeleton, or inhibition of the Rho kinase, did not block the PIP2 increase nor PIP5KIβ dephosphorylation. Therefore, PIP5KIβ is dephosphorylated in a volume-dependent manner by a calyculin A-sensitive protein phosphatase, which is activated upstream of actin remodeling and independently of Rho kinase activation. Our results establish a cause-and-effect relation between PIP5KIβ dephosphorylation, lipid kinase activation, and PIP2 increase in cells. This PIP2 increase can orchestrate multiple downstream responses, including the reorganization of the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)32630-32638
Number of pages9
JournalJournal of Biological Chemistry
Issue number43
StatePublished - Oct 27 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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