Protein Kinase C-dependent Tyrosine Phosphorylation of p130   in Differentiating Neuroblastoma Cells

Fagerström, Sofia; Påhlman, Sven; Nånberg, Eewa

doi:10.1074/jbc.273.4.2336

Cited by 34 publications

(21 citation statements)

References 47 publications

(49 reference statements)

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“…Cas forms appeared as a doublet with M r s of 110,000 and 120,000, with a low-abundance third form with an M r of 105,000 as previously observed by others (13,58). SHIP2 and tyrosine phosphorylated p130…”

Section: Interaction Of Ship2 With P130mentioning

confidence: 48%

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SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading

Prasad

Topping

Decker

2001

Molecular and Cellular Biology

126

128

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In a previous study, we found that the SHIP2 protein became tyrosine phosphorylated and associated with the Shc adapter protein in response to the treatment of cells with growth factors and insulin (T. Habib, J. A. Hejna, R. E. Moses, and S. J. Decker, J. Biol. Chem. 273:18605-18609, 1998). We describe here a novel interaction between SHIP2 and the p130Cas adapter protein, a mediator of actin cytoskeleton organization. SHIP2 and p130Cas association was detected in anti-SHIP2 immunoprecipitates from several cell types. Reattachment of trypsinized cells stimulated tyrosine phosphorylation of SHIP2 and increased the formation of a complex containing SHIP2 and a faster-migrating tyrosine-phosphorylated form of p130Cas . The fastermigrating form of p130Cas was no longer recognized by antibodies to the amino terminus of p130 Cas and appeared to be generated through proteolysis. Interaction of the SHIP2 protein with the various forms of p130Cas was mediated primarily through the SH2 domain of SHIP2. Immunofluorescence studies indicated that SHIP2 localized to focal contacts and to lamellipodia. Increased adhesion was observed in HeLa cells transiently expressing exogenous WT-SHIP2. These effects were not seen with SHIP2 possessing a mutation in the SH2 domain (R47G). Transfection of a catalytic domain deletion mutant of SHIP2 (⌬RV) inhibited cell spreading. Taken together, our studies suggest an important role for SHIP2 in adhesion and spreading.Products of phosphatidylinositol (PI) metabolism are important second messengers in cellular signaling pathways (1,11,70,76). Activation of PI 3Ј-kinase, which phosphorylates the 3Ј position of the inositol ring of PI, is a critical event in growth factor, insulin, and G protein-mediated signal transduction (14,25,49). In addition, PI 3Ј-kinase plays an important role in the regulation of adhesion and migration (68). PI 3Ј-kinase activation localizes to cell-cell and cell-matrix adhesion sites in epithelial cells, as well as to membrane ruffles in fibroblasts (78). Inhibition of PI 3Ј-kinase attenuated integrin-mediated adhesion and migration in several cell types, while expression of the catalytic p110 subunit of PI 3Ј-kinase enhanced cell adhesion (18,22,29,31,33,34,52,80). Moreover, p85, the regulatory subunit of PI 3Ј-kinase, interacted with proteins regulating adhesion and migration such as focal adhesion kinase (FAK) and p130Crk -associated substrate (p130 Cas ) (3,8,43).In vivo, the major substrate for PI 3Ј-kinase is phosphatidylinositol-4,5-bisphosphate [PI-(4,5)-P2] leading to the formation of phosphatidylinositol-3,4,5-trisphosphate [PI-(3,4,5)-P3] (63). Significant pools of phosphatidylinositol-3,4-bisphosphate [PI-(3,4)-P2] are also generated following PI 3Ј-kinase activation primarily through dephosphorylation of PI-(3,4,5)-P3 by 5Ј inositol phosphatases (27). PI-(3,4,5)-P3 and PI-(3,4)-P2 specifically interact with pleckstrin homology (PH) domains of proteins, regulating activity or intracellular localization of cellular enzymes such as Akt/PKB and its upstream k...

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Section: Interaction Of Ship2 With P130mentioning

confidence: 48%

“…Several distinct forms of p130 Cas have been previously observed (13,55,58). No functional distinction between these forms is currently known.…”

Section: This Study Describes a Novel Interaction Between Ship2 And P130mentioning

confidence: 99%

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading

Prasad

Topping

Decker

2001

Molecular and Cellular Biology

126

128

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“…A large series of growth factors have been shown to play a key role with still more to come (1) and the myriad of kinases makes signaling even more complex. Kinases involved in differentiation include protein kinases A and C (2)(3)(4), tyrosine receptor kinases trk A, B, C (5-9), MAP kinases (10)(11)(12)(13), Ca 2+ /calmodulin-dependent protein kinase (14,15), raf kinases (16,17), apoptosis signal-regulating kinase-1 (18), Src-related tyrosine kinase (19), orphan receptor serine/threonine kinase ALK7 (20), c-jun N-terminal kinases (21)(22)(23), extracellular signal-regulated kinases (24), LIM kinases (25) and kinase adaptor molecules (26).…”

Section: Introductionmentioning

confidence: 99%

Differentiation of Neuroblastoma Cell Line N1E-115 Involves Several Signaling Cascades

Karlmark

Shin

et al. 2005

Neurochem Res

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No systematic searches for differential expression of signaling proteins (SP) in undifferentiated vs. differentiated cell lineages were published and herein we used protein profiling for this purpose. The NIE-115 cell line was cultivated and an aliquot was differentiated with dimethylsulfoxide (DMSO), that is known to lead to a neuronal phenotype. Cell lysates were prepared, run on two-dimensional gel electrophoresis followed by MALDI-TOF-TOF identification of proteins and maps of identified SPs were generated. Seven SPs were comparable, 27 SPs: GTP-binding/Ras-related proteins, kinases, growth factors, calcium binding proteins, phosphatase-related proteins were observed in differentiated NIE-115 cells and eight SPs of the groups mentioned above were observed in undifferentiated cells only. Switching-on/off of several individual SPs from different signaling cascades during the differentiation process is a key to understand mechanisms involved. The findings reported herein are challenging in vitro and in vivo studies to confirm a functional role for deranged SPs.

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“…Cas/NEDD9 signaling networks are activated in response to a number of signaling molecules found within the tumor M Monographs microenvironment. Cas (and in many cases, NEDD9) becomes phosphorylated following stimulation with epidermal growth factor (EGF), 37 vascular endothelial growth factor (VEGF), 38,39 TGF-β, 25,40 insulin-like growth factor-1 (IGF-1), 41 hepatocyte growth factor (HGF), 42 bombesin, lysophosphatidic acid (LPA), and platelet-derived growth factor (PDGF). 43 An intact cytoskeleton is required for Cas phosphorylation following growth factor stimulation, as treatment with cytochalasin D abolishes the observed increase in tyrosine phosphorylation in response to EGF, bombesin, and PDGF.…”

Section: Tumor Progressionmentioning

confidence: 99%

Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton

2012

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The Cas family proteins, p130Cas (Cas) and NEDD9, are adaptor molecules that regulate cytoskeletal dynamics to promote multiple cellular processes, including migration, invasion, proliferation, and survival. Because these functions are also critical for tumor initiation, growth, and metastasis, Cas and NEDD9 are well positioned to contribute to these oncogenic processes. Indeed, mouse models of cancer show that these proteins function during multiple stages of disease progression. Furthermore, in many human cancers, high expression of Cas and NEDD9 is associated with advanced stage disease and is predictive of poor outcome. This review explores the contribution of Cas and NEDD9 during cellular transformation and neoplastic growth, tumor progression, metastasis, and the development of therapeutic resistance. Given these roles, Cas and NEDD9 may prove to be viable candidates for use as biomarkers and therapeutic targets.

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Protein Kinase C-dependent Tyrosine Phosphorylation of p130 in Differentiating Neuroblastoma Cells

Cited by 34 publications

References 47 publications

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading

Differentiation of Neuroblastoma Cell Line N1E-115 Involves Several Signaling Cascades

Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton

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Protein Kinase C-dependent Tyrosine Phosphorylation of p130 in Differentiating Neuroblastoma Cells

Cited by 34 publications

References 47 publications

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130CasAdapter Protein and Regulates Cellular Adhesion and Spreading

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130CasAdapter Protein and Regulates Cellular Adhesion and Spreading

Differentiation of Neuroblastoma Cell Line N1E-115 Involves Several Signaling Cascades

Cas and NEDD9 Contribute to Tumor Progression through Dynamic Regulation of the Cytoskeleton

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Product

Resources

About

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading

SH2-Containing Inositol 5′-Phosphatase SHIP2 Associates with the p130^CasAdapter Protein and Regulates Cellular Adhesion and Spreading