Phosphoinositide 3-kinase/Akt Pathway Mediates Fip1-like1-platelet-derived Growth Factor Receptor α-induced Cell Infiltration and Activation: Possible Molecular Mechanism for the Malignant Phenotype of Chronic Eosinophilic Leukemia

Phosphoinositide 3′-kinases constitute a family of lipid kinases implicated in signal transduction through tyrosine kinase receptors and heterotrimeric G protein-linked receptors. Phosphoinositide 3′-kinases that bind to the platelet-derived growth factor receptor are composed of two subunits: the p85 subunit acts as an adapter and couples the catalytic p110 subunit to the activated receptor. There are different isoforms of p85 as well as of p110, the individual roles of which have been elusive. Using microinjection of inhibitory antibodies specific for either p110(alpha) or p110(beta) we have investigated the involvement of the two p110 isoforms in platelet-derived growth factor- and insulin-induced actin reorganization in porcine aortic endothelial cells. We have found that antibodies against p110(alpha), but not antibodies against p110(beta), inhibit platelet-derived growth factor-stimulated actin reorganization, whereas the reverse is true for inhibition of insulin-induced actin reorganization. These data indicate that the two phosphoinositide 3′-kinase isoforms have distinct roles in signal transduction pathways induced by platelet-derived growth factor and insulin.

Download Full-text

Binding to the Platelet-derived Growth Factor Receptor Transiently Activates the p85α-p110α Phosphoinositide 3-Kinase Complexin Vivo

Journal of Biological Chemistry ◽

10.1074/jbc.271.35.21614 ◽

1996 ◽

Vol 271 (35) ◽

pp. 21614-21621 ◽

Cited By ~ 30

Author(s):

Jan Domin ◽

Ritu Dhand ◽

Michael D. Waterfield

Keyword(s):

Growth Factor ◽

Growth Factor Receptor ◽

Platelet Derived Growth Factor ◽

Phosphoinositide 3 Kinase

Download Full-text

Postnatal tendon growth and remodeling require platelet-derived growth factor receptor signaling

AJP Cell Physiology ◽

10.1152/ajpcell.00258.2017 ◽

2018 ◽

Vol 314 (4) ◽

pp. C389-C403 ◽

Cited By ~ 15

Author(s):

Kristoffer B. Sugg ◽

James F. Markworth ◽

Nathaniel P. Disser ◽

Andrew M. Rizzi ◽

Jeffrey R. Talarek ◽

...

Keyword(s):

Growth Factor ◽

Biological Activities ◽

Growth Factor Receptor ◽

Normal Growth ◽

Platelet Derived Growth Factor ◽

Growth And Remodeling ◽

Fibroblast Migration ◽

And Migration ◽

Phosphoinositide 3 Kinase

Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response. We demonstrate that both PDGFRs, PDGFRα and PDGFRβ, are expressed in tendon fibroblasts and that the inhibition of PDGFR signaling suppresses the normal growth of tendon tissue in response to mechanical growth cues due to defects in fibroblast proliferation and migration. We also identify membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for the migration of tendon fibroblasts through their extracellular matrix. Furthermore, we report that MT1-MMP translation is regulated by phosphoinositide 3-kinase/Akt signaling, while ERK1/2 controls posttranslational trafficking of MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these findings demonstrate that PDGFR signaling is necessary for postnatal tendon growth and remodeling and that MT1-MMP is a critical mediator of tendon fibroblast migration and a potential target for the treatment of tendon injuries and diseases.

Download Full-text