scholarly journals Insulin-like Growth Factor 1 Inhibits Apoptosis Using the Phosphatidylinositol 3′-Kinase and Mitogen-activated Protein Kinase Pathways

1997 ◽  
Vol 272 (1) ◽  
pp. 154-161 ◽  
Author(s):  
Marcelina Párrizas ◽  
Alan R. Saltiel ◽  
Derek LeRoith
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Mitogen Activated Protein ◽  
Phosphatidylinositol 3

scholarly journals Multiple Signaling Pathways of the Insulin-Like Growth Factor 1 Receptor in Protection from Apoptosis

1999 ◽  
Vol 19 (10) ◽  
pp. 7203-7215 ◽  
Author(s):  
Francesca Peruzzi ◽  
Marco Prisco ◽  
Michael Dews ◽  
Paolo Salomoni ◽  
Emanuela Grassilli ◽  
...  
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Like Growth Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Alternative Pathways ◽  
C Terminus ◽  
Mitogen Activated Protein

ABSTRACT The type 1 insulin-like growth factor receptor (IGF-1R), activated by its ligands, protects several cell types from a variety of apoptotic injuries. The main signaling pathway for IGF-1R-mediated protection from apoptosis has been previously elucidated and rests on the activation of phosphatidylinositol 3-kinase, Akt/protein kinase B, and the phosphorylation and inactivation of BAD, a member of the Bcl-2 family of proteins. In 32D cells (a murine hemopoietic cell line devoid of insulin receptor substrate 1 [IRS-1]), the IGF-1R activates alternative pathways for protection from apoptosis induced by withdrawal of interleukin-3. One of these pathways leads to the activation of mitogen-activated protein kinase, while a third pathway results in the mitochondrial translocation of Raf and depends on the integrity of a group of serines in the C terminus of the receptor that are known to interact with 14.3.3 proteins. All three pathways, however, result in BAD phosphorylation. The presence of multiple antiapoptotic pathways may explain the remarkable efficacy of the IGF-1R in protecting cells from apoptosis.

scholarly journals Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

2002 ◽  
Vol 277 (51) ◽  
pp. 49311-49318 ◽  
Author(s):  
Rodrigo Martinez ◽  
Flávia Carvalho Alcantara Gomes
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Ecm Proteins ◽  
Mitogen Activated Protein ◽  
Epidermal Growth ◽  
Phosphatidylinositol 3

Thyroid hormone (T3) plays a crucial role in several steps of cerebellar ontogenesis. By using a neuron-astrocyte coculture model, we have investigated the effects of T3-treated astrocytes on cerebellar neuronal differentiationin vitro. Neurons plated onto T3-astrocytes presented a 40–60% increase on the total neurite length and an increment in the number of neurites. Treatment of astrocytes with epidermal growth factor (EGF) yielded similar results, suggesting that this growth factor might mediate T3-induced neuritogenesis. EGF and T3 treatment increased fibronectin and laminin expression by astrocytes, suggesting that astrocyte neurite permissiveness induced by these treatments is mostly due to modulation of extracellular matrix (ECM) components. Such increase in ECM protein expression as well as astrocyte permissiveness to neurite outgrowth was reversed by the specific EGF receptor tyrosine kinase inhibitor, tyrphostin. Moreover, studies using selective inhibitors of several transduction-signaling cascades indicated that modulation of ECM proteins by EGF is mainly through a synergistic activation of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. In this work, we provide evidence of a novel role of EGF as an intermediary factor of T3 action on cerebellar ontogenesis. By modulating the content of ECM proteins, EGF increases neurite outgrowth. Our data reveal an important role of astrocytes as mediators of T3-induced cerebellar development and partially elucidate the role of EGF and mitogen-activated protein kinase/phosphatidylinositol 3-kinase pathways on this process.

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