Early signalling events of autophagy

2013 ◽  
Vol 55 ◽  
pp. 1-15 ◽  
Author(s):  
Laura E. Gallagher ◽  
Edmond Y.W. Chan
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mammalian Cells ◽  
Mammalian Target Of Rapamycin ◽  
Interacting Protein ◽  
The Core ◽  
Autophagy Gene ◽  
Autophagy Induction ◽  
Cellular Pathways

Autophagy is a conserved cellular degradative process important for cellular homoeostasis and survival. An early committal step during the initiation of autophagy requires the actions of a protein kinase called ATG1 (autophagy gene 1). In mammalian cells, ATG1 is represented by ULK1 (uncoordinated-51-like kinase 1), which relies on its essential regulatory cofactors mATG13, FIP200 (focal adhesion kinase family-interacting protein 200 kDa) and ATG101. Much evidence indicates that mTORC1 [mechanistic (also known as mammalian) target of rapamycin complex 1] signals downstream to the ULK1 complex to negatively regulate autophagy. In this chapter, we discuss our understanding on how the mTORC1–ULK1 signalling axis drives the initial steps of autophagy induction. We conclude with a summary of our growing appreciation of the additional cellular pathways that interconnect with the core mTORC1–ULK1 signalling module.

scholarly journals Focal Adhesion Kinase Suppresses Apoptosis by Binding to the Death Domain of Receptor-Interacting Protein

2004 ◽  
Vol 24 (10) ◽  
pp. 4361-4371 ◽  
Author(s):  
Elena Kurenova ◽  
Li-Hui Xu ◽  
Xihui Yang ◽  
Albert S. Baldwin ◽  
Rolf J. Craven ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Death Receptor ◽  
Human Tumors ◽  
Receptor Complex ◽  
Death Domain ◽  
Functional Link ◽  
Interacting Protein ◽  
Survival Signals

ABSTRACT Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine kinase that is overexpressed in a variety of human tumors, mediates one of these survival signals. Attenuation of FAK expression in tumor cells results in apoptosis that is mediated by caspase 8- and FADD-dependent pathways, suggesting that death receptor pathways are involved in the process. Here, we report a functional link between FAK and death receptors. We have demonstrated that FAK binds to the death domain kinase receptor-interacting protein (RIP). RIP is a major component of the death receptor complex and has been shown to interact with Fas and tumor necrosis factor receptor 1 through its binding to adapter proteins. We have shown that RIP provides proapoptotic signals that are suppressed by its binding to FAK. We thus propose that FAK overexpression in human tumors provides a survival signal function by binding to RIP and inhibiting its interaction with the death receptor complex.

Focal adhesion kinase, RhoA, and p38 mitogen‐activated protein kinase modulates apoptosis mediated by angiotensin II AT 2 receptors

2018 ◽  
Vol 120 (2) ◽  
pp. 1835-1849 ◽  
Author(s):  
María J. Manzur ◽  
Milton O. Aguilera ◽  
Mónica L. Kotler ◽  
Walter Berón ◽  
Gladys M. Ciuffo
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

scholarly journals FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells

2008 ◽  
Vol 181 (3) ◽  
pp. 497-510 ◽  
Author(s):  
Taichi Hara ◽  
Akito Takamura ◽  
Chieko Kishi ◽  
Shun-ichiro Iemura ◽  
Tohru Natsume ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Cellular Functions ◽  
Autophagosome Formation ◽  
Interacting Protein ◽  
Autophagy Induction ◽  
Negative Effect ◽  
And Migration ◽  
Starvation Conditions

Autophagy is a membrane-mediated intracellular degradation system. The serine/threonine kinase Atg1 plays an essential role in autophagosome formation. However, the role of the mammalian Atg1 homologues UNC-51–like kinase (ULK) 1 and 2 are not yet well understood. We found that murine ULK1 and 2 localized to autophagic isolation membrane under starvation conditions. Kinase-dead alleles of ULK1 and 2 exerted a dominant-negative effect on autophagosome formation, suggesting that ULK kinase activity is important for autophagy. We next screened for ULK binding proteins and identified the focal adhesion kinase family interacting protein of 200 kD (FIP200), which regulates diverse cellular functions such as cell size, proliferation, and migration. We found that FIP200 was redistributed from the cytoplasm to the isolation membrane under starvation conditions. In FIP200-deficient cells, autophagy induction by various treatments was abolished, and both stability and phosphorylation of ULK1 were impaired. These results suggest that FIP200 is a novel mammalian autophagy factor that functions together with ULKs.

scholarly journals Protein Kinase C Activation Stimulates Mesenchymal Stem Cell Adhesion through Activation of Focal Adhesion Kinase

2013 ◽  
Vol 22 (5) ◽  
pp. 797-809 ◽  
Author(s):  
Byeong-Wook Song ◽  
Woochul Chang ◽  
Bum-Kee Hong ◽  
Il-Kwon Kim ◽  
Min-Ji Cha ◽  
...  
Keyword(s):  
Stem Cell ◽  
Protein Kinase C ◽  
Cell Adhesion ◽  
Protein Kinase ◽  
Mesenchymal Stem Cell ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Kinase C ◽  
Protein Kinase C Activation

Activation of focal adhesion kinase by protein kinase Cϵ in neonatal rat ventricular myocytes

2003 ◽  
Vol 285 (4) ◽  
pp. H1684-H1696 ◽  
Author(s):  
Maria C. Heidkamp ◽  
Allison L. Bayer ◽  
Brian T. Scully ◽  
Diane M. Eble ◽  
Allen M. Samarel
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Protein Tyrosine Kinase ◽  
Coiled Coil ◽  
Signal Transduction Pathway ◽  
Dominant Negative ◽  
Neonatal Rat ◽  
Cardiomyocyte Hypertrophy ◽  
Cofilin Phosphorylation

Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase critical for both cardiomyocyte survival and sarcomeric assembly during endothelin (ET)-induced cardiomyocyte hypertrophy. ET-induced FAK activation requires upstream activation of one or more isoenzymes of protein kinase C (PKC). Therefore, with the use of replication-defective adenoviruses (Adv) to overexpress constitutively active (ca) and dominant negative (dn) mutants of PKCs, we examined which PKC isoenzymes are necessary for FAK activation and which downstream signaling components are involved. FAK activation was assessed by Western blot analysis with an antibody specific for FAK autophosphorylated at Y397 (Y397pFAK). ET (10 nmol/l; 2–30 min) resulted in the time-dependent activation of FAK which was inhibited by chelerythrine (5 μmol/l; 1 h pretreatment). Adv-caPKCϵ, but not Adv-caPKCδ, activated FAK compared with a control Adv encoding β-galactosidase. Conversely, Adv-dnPKCϵ inhibited ET-induced FAK activation. Y-27632 (10 μmol/l; 1 h pretreatment), an inhibitor of Rho-associated coiled-coil-containing protein kinases (ROCK), prevented ET- and caPKCϵ-induced FAK activation as well as cofilin phosphorylation. Pretreatment with cytochalasin D (1 μmol/l, 1 h pretreatment) also inhibited ET-induced Y397pFAK and cofilin phosphorylation and caPKCϵ-induced Y397pFAK. Neither inhibitor, however, interfered with ET-induced ERK1/2 activation. Finally, PP2 (50 μmol/l; 1 h pretreatment), a highly selective Src inhibitor, did not alter basal or ET-induced Y397pFAK. PP2 did, however, reduce basal and ET-induced phosphorylation of other sites on FAK, namely, Y576, Y577, Y861, and Y925. We conclude that the ET-induced signal transduction pathway resulting in downstream Y397pFAK is partially dependent on PKCϵ, ROCK, cofilin, and assembled actin filaments, but not ERK1/2 or Src.

Focal Adhesion Kinase and Protein Kinase B Cooperate to Suppress Doxorubicin-Induced Apoptosis of Breast Tumor Cells

2006 ◽  
Vol 70 (4) ◽  
pp. 1330-1339 ◽  
Author(s):  
Maroesja J. van Nimwegen ◽  
Merei Huigsloot ◽  
Annamarie Camier ◽  
Ine B. Tijdens ◽  
Bob van de Water
Keyword(s):  
Protein Kinase ◽  
Focal Adhesion Kinase ◽  
Tumor Cells ◽  
Focal Adhesion ◽  
Breast Tumor ◽  
Protein Kinase B ◽  
Breast Tumor Cells ◽  
Induced Apoptosis
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