Production of PtdInsP3 at endomembranes is triggered by receptor endocytosis.

Abstract

Phosphatidylinositol-3,4,5-trisphosphate (PtdInsP(3)) regulates diverse cellular functions, including cell proliferation and apoptosis, and has roles in the progression of diabetes and cancer. However, little is known about its production. Here, we describe fluorescent indicators for PtdInsP(3) that allow a spatio-temporal examination of PtdInsP(3) production in single living cells. After ligand stimulation, PtdInsP(3) levels increased to a larger extent at the endomembranes (that is, the endoplasmic reticulum and the Golgi) than at the plasma membrane. This increase was found to originate from in situ production at the endomembranes, a process stimulated directly by receptor tyrosine kinases endocytosed from the plasma membrane to the endomembranes. The demonstration of PtdInsP(3) production through receptor endocytosis addresses a long-standing question about how signalling pathways downstream of PtdInsP(3) are activated at intracellular compartments remote from the plasma membrane.

• Authors: Moritoshi Sato, Yoshibumi Ueda, Tokio Takagi, Yoshio Umezawa
• Journal: Nature cell biology (Nat Cell Biol) Vol. 5 Issue 11 Pg. 1016-22 (Nov 2003) ISSN: 1465-7392 [Print] England
• PMID: 14528311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorescent Dyes
• Phosphatidylinositol Phosphates
• phosphatidylinositol 3,4,5-triphosphate
• Receptors, Platelet-Derived Growth Factor

Topics

• Amino Acid Sequence
• Animals
• CHO Cells
• Cricetinae
• Endocytosis
• Fluorescent Dyes
• Intracellular Membranes (metabolism)
• Phosphatidylinositol Phosphates (biosynthesis)
• Receptors, Platelet-Derived Growth Factor (metabolism)