The class II phosphoinositide 3-kinase PI3K-C2β regulates cell migration by a PtdIns(3)P dependent mechanism

2005 ◽  
Vol 205 (3) ◽  
pp. 452-462 ◽  
Author(s):  
Jan Domin ◽  
Lisa Harper ◽  
Deborah Aubyn ◽  
Matthew Wheeler ◽  
Oliver Florey ◽  
...  
Keyword(s):  
Cell Migration ◽  
Class Ii ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

scholarly journals Migrating fibroblasts reorient directionality by a metastable, PI3K-dependent mechanism

2012 ◽  
Vol 197 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Erik S. Welf ◽  
Shoeb Ahmed ◽  
Heath E. Johnson ◽  
Adam T. Melvin ◽  
Jason M. Haugh
Keyword(s):  
Cell Migration ◽  
Total Internal Reflection ◽  
Mesenchymal Cell ◽  
Lateral Spreading ◽  
Pi3k Signaling ◽  
Spatial Cues ◽  
Cell Protrusion ◽  
Pi3k Inhibition ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

Mesenchymal cell migration as exhibited by fibroblasts is distinct from amoeboid cell migration and is characterized by dynamic competition among multiple protrusions, which determines directional persistence and responses to spatial cues. Localization of phosphoinositide 3-kinase (PI3K) signaling is thought to play a broadly important role in cell motility, yet the context-dependent functions of this pathway have not been adequately elucidated. By mapping the spatiotemporal dynamics of cell protrusion/retraction and PI3K signaling monitored by total internal reflection fluorescence microscopy, we show that randomly migrating fibroblasts reorient polarity through PI3K-dependent branching and pivoting of protrusions. PI3K inhibition did not affect the initiation of newly branched protrusions, nor did it prevent protrusion induced by photoactivation of Rac. Rather, PI3K signaling increased after, not before, the onset of local protrusion and was required for the lateral spreading and stabilization of nascent branches. During chemotaxis, the branch experiencing the higher chemoattractant concentration was favored, and, thus, the cell reoriented so as to align with the external gradient.

scholarly journals Phosphoinositide 3-Kinase C2β Regulates Cytoskeletal Organization and Cell Migration via Rac-dependent Mechanisms

2006 ◽  
Vol 17 (9) ◽  
pp. 3729-3744 ◽  
Author(s):  
Roy M. Katso ◽  
Olivier E. Pardo ◽  
Andrea Palamidessi ◽  
Clemens M. Franz ◽  
Marin Marinov ◽  
...  
Keyword(s):  
Cell Migration ◽  
Molecular Mechanisms ◽  
Egf Receptor ◽  
Human Tumor ◽  
Class Ii ◽  
Dominant Negative ◽  
Class I ◽  
Membrane Ruffling ◽  
And Migration ◽  
Phosphoinositide 3 Kinase

Receptor-linked class I phosphoinositide 3-kinases (PI3Ks) induce assembly of signal transduction complexes through protein–protein and protein–lipid interactions that mediate cell proliferation, survival, and migration. Although class II PI3Ks have the potential to make the same phosphoinositides as class I PI3Ks, their precise cellular role is currently unclear. In this report, we demonstrate that class II phosphoinositide 3-kinase C2β (PI3KC2β) associates with the Eps8/Abi1/Sos1 complex and is recruited to the EGF receptor as part of a multiprotein signaling complex also involving Shc and Grb2. Increased expression of PI3KC2β stimulated Rac activity in A-431 epidermoid carcinoma cells, resulting in enhanced membrane ruffling and migration speed of the cells. Conversely, expression of dominant negative PI3KC2β reduced Rac activity, membrane ruffling, and cell migration. Moreover, PI3KC2β-overexpressing cells were protected from anoikis and displayed enhanced proliferation, independently of Rac function. Taken together, these findings suggest that PI3KC2β regulates the migration and survival of human tumor cells by distinct molecular mechanisms.

scholarly journals Class II phosphoinositide 3-kinase defines a novel signaling pathway in cell migration

2005 ◽  
Vol 169 (5) ◽  
pp. 789-799 ◽  
Author(s):  
Tania Maffucci ◽  
Frank T. Cooke ◽  
Fiona M. Foster ◽  
Colin J. Traer ◽  
Michael J. Fry ◽  
...  
Keyword(s):  
Cell Migration ◽  
Signaling Pathway ◽  
Lysophosphatidic Acid ◽  
Second Messenger ◽  
Cellular Responses ◽  
Class Ii ◽  
Downstream Effectors ◽  
Phosphoinositide 3 Kinase ◽  
Precise Role

The lipid products of phosphoinositide 3-kinase (PI3K) are involved in many cellular responses such as proliferation, migration, and survival. Disregulation of PI3K-activated pathways is implicated in different diseases including cancer and diabetes. Among the three classes of PI3Ks, class I is the best characterized, whereas class II has received increasing attention only recently and the precise role of these isoforms is unclear. Similarly, the role of phosphatidylinositol-3-phosphate (PtdIns-3-P) as an intracellular second messenger is only just beginning to be appreciated. Here, we show that lysophosphatidic acid (LPA) stimulates the production of PtdIns-3-P through activation of a class II PI3K (PI3K-C2β). Both PtdIns-3-P and PI3K-C2β are involved in LPA-mediated cell migration. This study is the first identification of PtdIns-3-P and PI3K-C2β as downstream effectors in LPA signaling and demonstration of an intracellular role for a class II PI3K. Defining this novel PI3K-C2β–PtdIns-3-P signaling pathway may help clarify the process of cell migration and may shed new light on PI3K-mediated intracellular events.

The P2Y12receptor induces platelet aggregation through weak activation of the αIIbβ3integrin - a phosphoinositide 3-kinase-dependent mechanism

FEBS Letters ◽  
2001 ◽  
Vol 505 (2) ◽  
pp. 281-290 ◽  
Author(s):  
G. Kauffenstein ◽  
W. Bergmeier ◽  
A. Eckly ◽  
P. Ohlmann ◽  
C. Léon ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Phosphoinositide 3 Kinase ◽  
Dependent Mechanism

scholarly journals A p53-Phosphoinositide Signalosome Regulates Nuclear Akt Activation

2021 ◽  
Author(s):  
Mo Chen ◽  
Suyong Choi ◽  
Tianmu Wen ◽  
Changliang Chen ◽  
Narendra Thapa ◽  
...  
Keyword(s):  
Genotoxic Stress ◽  
Akt Pathway ◽  
Mutant P53 ◽  
Tumor Suppressor P53 ◽  
Wild Type ◽  
Akt Activation ◽  
Pi3k Inhibitors ◽  
Phosphoinositide 3 Kinase ◽  
Induced Apoptosis ◽  
Dependent Mechanism

The tumor suppressor p53 and the phosphoinositide 3-kinase (PI3K)-Akt pathway have fundamental roles in regulating cell growth, apoptosis and are frequently mutated in cancer. Here, we show that genotoxic stress induces nuclear Akt activation by a p53-dependent mechanism that is independent from the canonical membrane-localized PI3K-Akt pathway. Upon genotoxic stress a nuclear p53-PI3,4,5P3 complex is generated in regions devoid of membranes by a nuclear PI3K, and this complex recruits all the kinases required to activate Akt and phosphorylate FOXOs, inhibiting DNA damage-induced apoptosis. Wild-type p53 activates nuclear Akt in an on/off fashion upon stress, whereas mutant p53 stimulates high basal Akt activity, indicating a fundamental difference. The nuclear p53-phosphoinositide signalosome is distinct from the canonical membrane-localized pathway and insensitive to PI3K inhibitors currently in the clinic, underscoring its therapeutic relevance.

scholarly journals The HU177 Collagen Epitope Controls Melanoma Cell Migration and Experimental Metastasis by a CDK5/YAP-Dependent Mechanism

2018 ◽  
Vol 188 (10) ◽  
pp. 2356-2368 ◽  
Author(s):  
Jennifer M. Caron ◽  
XiangHua Han ◽  
Liangru Contois ◽  
Calvin P.H. Vary ◽  
Peter C. Brooks
Keyword(s):  
Cell Migration ◽  
Melanoma Cell ◽  
Experimental Metastasis ◽  
Dependent Mechanism

scholarly journals Interleukin-8 Induces the Endothelial Cell Migration through the Activation of Phosphoinositide 3-Kinase-Rac1/RhoA Pathway

2011 ◽  
Vol 7 (6) ◽  
pp. 782-791 ◽  
Author(s):  
Yi Lai ◽  
Yang Shen ◽  
Xiao-Heng Liu ◽  
Yi Zhang ◽  
Ye Zeng ◽  
...  
Keyword(s):  
Cell Migration ◽  
Endothelial Cell ◽  
Interleukin 8 ◽  
Endothelial Cell Migration ◽  
Phosphoinositide 3 Kinase

New insight into the intracellular roles of class II phosphoinositide 3-kinases

2014 ◽  
Vol 42 (5) ◽  
pp. 1378-1382 ◽  
Author(s):  
Tania Maffucci ◽  
Marco Falasca
Keyword(s):  
Class Ii ◽  
Present Review ◽  
Phosphoinositide 3 Kinase ◽  
Redundant Role ◽  
Insight Into

In the last few years, an increased attention to class II isoforms of phosphoinositide 3-kinase (PI3K) has emerged, mainly fuelled by evidence suggesting a distinct non-redundant role for these enzymes compared with other PI3Ks. Despite this renewed interest, many questions remain on the specific functions regulated by these isoforms and their mechanism of activation and action. In the present review, we discuss results from recent studies that have provided some answers to these questions.

Sign in / Sign up

Export Citation Format

Share Document