Massive Actin Polymerization Induced by Phosphatidylinositol-4-phosphate 5-Kinase in Vivo

Shibasaki, Yoshikazu; Ishihara, Hideharu; Kizuki, Nobuaki; Asano, Tomohiko; Oka, Yoshitomo; Yazaki, Yoshio

doi:10.1074/jbc.272.12.7578

Cited by 170 publications

(139 citation statements)

References 28 publications

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“…At the downstream of RhoA, Ser/Thr kinases Rhoassociated coiled-coil protein kinase (ROCK) and phosphatidylinositol-4-phosphate-5-kinase (PI4P5K) have been shown to regulate ERM phosphorylation and its interactions (Shibasaki et al, 1997;Matsui et al, 1999;Saci and Carpenter, 2005). Moreover, Rho-PI4P5K-PIP 2 pathway is responsible for continuous activation of ERM proteins.…”

Section: Rhoa-pi4p5k-pip 2 Pathway Mediates Cd146-induced Erm Activationmentioning

confidence: 99%

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

et al. 2011

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Tumor cell migration is a well-orchestrated multistep process that drives cancer development and metastasis. Previous data indicated that CD146 expression correlates with malignant progression and metastatic potential of human melanoma cells. However, the exact molecular mechanism of how CD146 promotes melanoma cell migration still remains poorly understood. Here, we report that CD146 physically interacts with actin-linking ezrin-radixin-moesin (ERM) proteins and recruits ERM proteins to cell protrusions, promoting the formation and elongation of microvilli. Moreover, CD146-promoted melanoma cell migration is linked to RhoA activation and ERM phosphorylation. CD146 recruits Rho guanine nucleotide dissociation inhibitory factors 1 (RhoGDI1) through ERM proteins and thus sequesters RhoGDI1 from RhoA, which leads to upregulated RhoA activity and increased melanoma cell motility. CD146-activated RhoA also promotes further ERM phosphorylation and activation through Rho-phosphatidylinositol-4-phosphate-5-kinase-phosphatidylinositol 4,5-biphosphate pathway, which reinforces CD146/ERM association. Thus, our results provide a mechanistic basis to understand the role of CD146 in regulating human melanoma cell motility.

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Section: Rhoa-pi4p5k-pip 2 Pathway Mediates Cd146-induced Erm Activationmentioning

confidence: 99%

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

et al. 2011

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“…These enzymes can be precipitated in complexes that contain the small G proteins Rho and Rac (46,289,355), although it is not known if this is a direct interaction or involves additional proteins. PtdIns(4,5)P 2 is an important regulator of the actin cytoskeleton, and overexpression of PIP5KIB causes massive actin polymerization that is not prevented by coexpression of a dominant negative form of RhoA, suggesting that the lipid kinase is downstream of Rho (316). Recently an activator of PIP5KIB was purified and found to be the small G protein Arf1 (151).…”

Section: Pip5ki␣ Pip5ki␤ Pip5ki␥ and Mss4pmentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

265

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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“…Neural tube closure requires numerous cellular events, including extensive cell movement. Given the speculated role of PIP5KI␥ in actin dynamics and focal adhesion formation (10,11,18), we analyzed whether neuronal cells derived from knockout embryos exhibited normal ex vivo migration. Using a modified Boyden chamber, we found a 50% reduction in PIP5KI␥-null neuronal precursor cell migration across a matrigel-coated filter after 24 h, compared to cells derived from wild-type littermates (Fig.…”

Section: Loss Of Pip5ki␥ Leads To Embryonic Lethality At Embryonic Damentioning

confidence: 99%

PIP5KIγ is required for cardiovascular and neuronal development

Wang

Lian²,

Golden³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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All eukaryotic cells contain the phospholipid phosphatidylinositol 4, 5-bisphosphate (PIP2) that serves multiple roles in signal transduction cascades. Type I phosphatidylinositol-4-phosphate 5-kinase (PIP5KI) catalyzes the synthesis of PIP2 by phosphorylating phosphatidylinositol 4 phosphate. Although the classical isoforms of PIP5KI (designated as ␣, ␤, and ␥) all generate the same phospholipid product, they have significantly dissimilar primary structures and expression levels in different tissues, and they appear to localize within different compartments within the cell. Therefore, it appears likely that PIP5KI isoforms have overlapping, but not identical, functions. Here we show that targeted disruption of PIP5KI␥ causes widespread developmental and cellular defects. PIP5KI␥-null embryos have myocardial developmental defects associated with impaired intracellular junctions that lead to heart failure and extensive prenatal lethality at embryonic day 11.5 of development. Loss of PIP5KI␥ also results in neural tube closure defects that were associated with impaired PIP2 production, adhesion junction formation, and neuronal cell migration. These data, along with those of other PIP5KI isoforms, indicate that individual PIP5KI isoenzymes fulfill specific roles in embryonic development.phosphoinositide ͉ phospholipid ͉ phosphatidylinositol 4,5-bisphosphate

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Massive Actin Polymerization Induced by Phosphatidylinositol-4-phosphate 5-Kinase in Vivo

Cited by 170 publications

References 28 publications

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

Recognition of CD146 as an ERM-binding protein offers novel mechanisms for melanoma cell migration

Phosphoinositides in Constitutive Membrane Traffic

PIP5KIγ is required for cardiovascular and neuronal development

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