ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation

  title={ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation},
  author={Joffrey L. Degoutin and Marc Vigny and Jean Y Gouzi},
  journal={FEBS Letters},
Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells
The results suggest that ALK activation of Rap1 may contribute to cell proliferation and oncogenesis of neuroblastoma driven by gain-of-function mutant ALK receptors.
Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells
It is shown here that activated ALK robustly activates STAT3 on Tyr705 in a number of independent neuroblastoma cell lines, and knockdown of STAT3 by RNA interference resulted in a reduction in myelocytomatosis neuroblastom (MYCN) protein levels downstream of ALK signaling.
Integrated proximal proteomics reveals IRS2 as a determinant of cell survival in ALK-driven neuroblastoma
The IPP analysis provides insight into the proximal architecture of oncogenic ALK signaling by revealing IRS2 as an adaptor protein that links ALK to neuroblastoma cell survival through the Akt-FoxO3 signaling axis.
Anaplastic lymphoma kinase: signalling in development and disease
The role of ALK in development and disease is addressed, implications for the future are discussed and many chromosomal rearrangements leading to enhanced ALK activity are described.
Regulation of growth factor signaling by FRS2 family docking/scaffold adaptor proteins
  • N. Gotoh
  • Biology, Chemistry
    Cancer science
  • 2008
The involvement of FRS2 proteins in tumorigenesis should be studied extensively to be validated as candidate biomarkers for the effectiveness of treatments targeting RTKs such as the FGF receptor and EGF receptor.
The Receptor Tyrosine Kinase Alk Controls Neurofibromin Functions in Drosophila Growth and Learning
dAlk is identified as an upstream activator of dNf1-regulated Ras signaling responsible for several dNF1 defects, and human Alk is implicate as a potential therapeutic target in NF1.
The Tyrosine Phosphatase hPTPRβ Controls the Early Signals and Dopaminergic Cells Viability via the P2X7 Receptor
It is demonstrated that the neuronal response to purinergic stimulation involves the Calmodulin/RasGRF1 activation of the small GTPase Ras and Erk1/2, and that tyrosine phosphatase PTPRβ and other tyrosin phosphatases regulate the smallGTPase activation pathway and neuronal viability.
Frs2α enhances fibroblast growth factor-mediated survival and differentiation in lens development
Most growth factor receptor tyrosine kinases (RTKs) signal through similar intracellular pathways, but they often have divergent biological effects. Therefore, elucidating the mechanism of channeling
Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2
Results indicate that the higher binding activity of the phosphorylation-independent binding site in NPM-ALK is caused by additional hydrophobic interactions, which are much broader and more extensive than those of the phosphate-dependent binding sites.
Activation of the orphan receptor tyrosine kinase ALK by zinc.


Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines
ALK-ShcC signal activation, possibly caused by co-amplification with the N-myc gene, might give additional effects on malignant tumor progression of neuroblastoma.
Role of the subcellular localization of ALK tyrosine kinase domain in neuronal differentiation of PC12 cells
It is demonstrated that membrane attachment of the ALK PTK domain, in PC12 cells, is crucial for initiation of neurite outgrowth and proliferation arrest through a decrease of DNA synthesis and it is shown that this differentiation process relies on specific and sustained activation of ERK 1/2 proteins.
Anaplastic Lymphoma Kinase Is a Dependence Receptor Whose Proapoptotic Functions Are Activated by Caspase Cleavage
It is shown that Jurkat cells overexpressing the wild-type ALK receptor are more sensitive to doxorubicin-induced apoptosis than parental cells, and the ALK protein is cleaved during apoptosis in a caspase-dependent manner, placing it in the growing family of dependence receptors.
Activation of Anaplastic Lymphoma Kinase Receptor Tyrosine Kinase Induces Neuronal Differentiation through the Mitogen-activated Protein Kinase Pathway*
Analysis of the signaling pathways involved in this process pointed to an essential role of the mitogen-activated protein kinase cascade, consistent with a role for ALK in neuronal differentiation.
Multiple Effector Domains within SNT1 Coordinate ERK Activation and Neuronal Differentiation of PC12 Cells*
Differentiation of neuronal precursor cells in response to neurotrophic differentiation factors is accompanied by the activation of membrane-anchored SNT signaling adaptor proteins. Two classes of
The ShcA phosphotyrosine docking protein sensitizes cardiovascular signaling in the mouse embryo.
ShcA is primarily expressed in the cardiovascular system during early mouse embryogenesis and regulates both heart development and establishment of mature blood vessels, and may orchestrate complex interactions within the vascular compartment by rendering cells permissive to respond to soluble and adhesive external cues.
ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth
It is shown that mAb16-39 elicits tyrosine phosphorylation of endogenously expressed ALK in human neuroblastoma (SK-N-SH) cells, indicating an essential role of the mitogen-activated protein kinase (MAP kinase) signaling cascade in ALK-mediated growth and differentiation of neurons.
The Signaling Adapter FRS-2 Competes with Shc for Binding to the Nerve Growth Factor Receptor TrkA
It is demonstrated that overexpression of FRS-2 in cells expressing an NGF nonresponsive TrkA receptor mutant reconstitutes the ability of NGF to stop cell cycle progression and to stimulate neuronal differentiation.
Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction
The results suggest that tyrosine 1062 in RET provides a site for the interaction of multiple signaling molecules and that the balance of SHC and SNT/FRS2 binding may affect the nature of the intracellular signaling for cell proliferation, differentiation and survival induced by activated RET.