NDLI: LL5β Directs the Translocation of Filamin A and SHIP2 to Sites of Phosphatidylinositol 3,4,5-Triphosphate (PtdIns(3,4,5)P3) Accumulation, and PtdIns(3,4,5)P3 Localization Is Mutually Modified by Co-recruited SHIP2*

Content Provider	PubMed Central
Author	Takabayashi, Tetsuji Xie, Min-jue Takeuchi, Seiji Kawasaki, Motomi Yagi, Hideshi Okamoto, Masayuki Tariqur, Rahman M. Malik, Fawzia Kuroda, Kazuki Kubota, Chikara Fujieda, Shigeharu Nagano, Takashi Sato, Makoto
Abstract	Phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) accumulates at the leading edge of migrating cells and works, at least partially, as both a compass to indicate directionality and a hub for subsequent intracellular events. However, how PtdIns(3,4,5)P3 regulates the migratory machinery has not been fully elucidated. Here, we demonstrate a novel mechanism for efficient lamellipodium formation that depends on PtdIns(3,4,5)P3 and the reciprocal regulation of PtdIns(3,4,5)P3 itself. LL5β, whose subcellular localization is directed by membrane PtdIns(3,4,5)P3, recruits the actin-cross-linking protein Filamin A to the plasma membrane, where PtdIns(3,4,5)P3 accumulates, with the Filamin A-binding Src homology 2 domain-containing inositol polyphosphate 5-phosphatase 2 (SHIP2). A large and dynamic lamellipodium was formed in the presence of Filamin A and LL5β by the application of epidermal growth factor. Conversely, depletion of either Filamin A or LL5β or the overexpression of either an F-actin-cross-linking mutant of Filamin A or a mutant of LL5β without its PtdIns(3,4,5)P3-interacting region inhibited such events in COS-7 cells. Because F-actin initially polymerizes near the plasma membrane, it is likely that membrane-recruited Filamin A efficiently cross-links newly polymerized F-actin, leading to enhanced lamellipodium formation at the site of PtdIns(3,4,5)P3 accumulation. Moreover, we demonstrate that co-recruited SHIP2 dephosphorylates PtdIns(3,4,5)P3 at the same location.
Related Links	http://dx.doi.org/10.1074/jbc.m109.081901
Ending Page	16165
Page Count	11
Starting Page	16155
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	21
Volume Number	285
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-05-21
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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LL5β Directs the Translocation of Filamin A and SHIP2 to Sites of Phosphatidylinositol 3,4,5-Triphosphate (PtdIns(3,4,5)P3) Accumulation, and PtdIns(3,4,5)P3 Localization Is Mutually Modified by Co-recruited SHIP2

LL5β Is a Phosphatidylinositol (3,4,5)-Trisphosphate Sensor That Can Bind the Cytoskeletal Adaptor, γ-Filamin

Stereo-specific Substrate Recognition by Phosphatidylinositol Phosphate Kinases Is Swapped by Changing a Single Amino Acid Residue

A Novel, Rapid, and Highly Sensitive Mass Assay for Phosphatidylinositol 3,4,5-Trisphosphate (PtdIns(3,4,5)P3) and Its Application to Measure Insulin-stimulated PtdIns(3,4,5)P3 Production in Rat Skeletal Muscle in Vivo

Localization of agonist-sensitive PtdIns(3,4,5)P3 reveals a nuclear pool that is insensitive to PTEN expression

Accumulation of PtdIns(3,4)P2 and PtdIns(3,4,5)P3 in thrombin-stimulated platelets. Different sensitivities to Ca2+ or functional integrin.

Distinct Classes of Phosphatidylinositol 3′-Kinases Are Involved in Signaling Pathways That Control Macroautophagy in HT-29 Cells

Membrane recruitment of DOCK180 by binding to PtdIns(3,4,5)P3.

Activation of protein kinase C family members by the novel polyphosphoinositides PtdIns-3,4-P2 and PtdIns-3,4,5-P3.

LL5β Directs the Translocation of Filamin A and SHIP2 to Sites of Phosphatidylinositol 3,4,5-Triphosphate (PtdIns(3,4,5)P3) Accumulation, and PtdIns(3,4,5)P3 Localization Is Mutually Modified by Co-recruited SHIP2*

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LL5β Directs the Translocation of Filamin A and SHIP2 to Sites of Phosphatidylinositol 3,4,5-Triphosphate (PtdIns(3,4,5)P3) Accumulation, and PtdIns(3,4,5)P3 Localization Is Mutually Modified by Co-recruited SHIP2

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LL5β Directs the Translocation of Filamin A and SHIP2 to Sites of Phosphatidylinositol 3,4,5-Triphosphate (PtdIns(3,4,5)P3) Accumulation, and PtdIns(3,4,5)P3 Localization Is Mutually Modified by Co-recruited SHIP2*