The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway

Dolfi, Fabrizio; García-Guzmán, Miguel; Ojaniemi, Marja; Nakamura, Hitoshi; Vuori, Kristiina

doi:10.1073/pnas.95.26.15394

Cited by 168 publications

(166 citation statements)

References 43 publications

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“…Paxillin is an adapter molecule that can link FAK to multiple pathways (Deakin and Turner, 2008). The N-terminus of paxillin contains two phosphorylation sites, tyrosines 31 and 118, which bind Crk and can control Ras and ERK signalling (Dolfi et al, 1998;Igishi et al, 1999). Mutation of tyrosines 31 and 118 to phenylalanine block Crk-mediated fibroblast migration (Petit et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Zouq

Keeble

Lindsay

et al. 2009

Journal of Cell Science

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survival signalling in cell types from distinct embryonic lineages that show differing sensitivities to anoikis. We demonstrate that both fibroblasts and epithelial cells prevent anoikis through FAK activation. We show that FAK activates multiple downstream pathways in order to suppress anoikis. However FAK regulates survival through a more restricted set of pathways in the more anoikis-sensitive epithelial cells. Furthermore, we identify a novel role for paxillin in apoptosis suppression.

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Section: Discussionmentioning

confidence: 99%

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Zouq

Keeble

Lindsay

et al. 2009

Journal of Cell Science

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“…In fact, the phosphorylation of FAK and paxillin can be elicited in cultured cells by cyclical mechanical strain (Yano et al, 1996;Smith et al, 1997Smith et al, ,1998. FAK has been proposed to couple integrins and cytoskeletal proteins to multiple signaling pathways In addition, several lines of evidence suggest that FAK is required for stress stimulation to activate MAP kinase pathways including JNK cascades (Dolfi et al, 1998;Schlaepfer and Hunter, 1998;Zhao et al, 1998;King et al, 1999;Almeida et al, 2000). On the other hand, scaffold protein MEKK1, an upstream mitogen activated protein kinase K (MAPKK) kinase of JNK cascades, is also associated with cytoskeleton reorganization and activated in response to cell volume changes (Kwan et al, 2001;Cross and Templeton, 2004;Lieber et al, 2004).…”

Section: Future Developmentsmentioning

confidence: 99%

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

2006

Progress in Retinal and Eye Research

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One of the functional roles of the corneal epithelial layer is to protect the cornea, lens and other underlying ocular structures from damages caused by environmental insults. It is important for corneal epithelial cells to maintain this function by undergoing continuous renewal through a dynamic process of wound healing. Previous studies in corneal epithelial cells have provided substantial evidence showing that environmental insults, such as ultraviolet (UV) irradiation and other biohazards, can induce stress-related cellular responses resulting in apoptosis and thus interrupt the dynamic process of wound healing. We found that UV irradiation-induced apoptotic effects in corneal epithelial cells are started by the hyperactivation of K + channels in the cell membrane resulting in a fast loss of intracellular K + ions. Recent studies provide further evidence indicating that these complex responses in corneal epithelial cells are resulted from the activation of stressrelated signaling pathways mediated by K + channel activity. The effect of UV irradiation on corneal epithelial cell fate shares common signaling mechanisms involving the activation of intracellular responses that are often activated by the stimulation of various cytokines. One piece of evidence for making this distinction is that at early times UV irradiation activates a Kv3.4 channel in corneal epithelial cells to elicit activation of c-Jun N-terminal kinase cascades and p53 activation leading to cell cycle arrest and apoptosis. The hypothetic model is that UV-induced potassium channel hyperactivity as an early event initiates fast cell shrinkages due to the loss of intracellular potassium, resulting in the activation of scaffolding protein kinases and cytoskeleton reorganizations. This review article presents important control mechanisms that determine Kv channel activity-mediated cellular responses in corneal epithelial cells, involving activation of stress-induced signaling pathways, arrests of cell cycle progression and/or induction of apoptosis.

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“…Likewise, human CRK proteins also lack catalytic activity, but are critically important for signal propagation along multiple pathways. Previous studies have ascribed CRKI and CRKII's signaling activity to direct association with other signaling proteins including p 130CAS , C3G, JNK1, paxillin, and HPK1 (Tanaka et al, 1997;Dolfi et al, 1998;Klemke et al, 1998;Oehrl et al, 1998;Petit et al, 2000;Girardin and Yaniv, 2001).…”

Section: Introductionmentioning

confidence: 99%

Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas

et al. 2003

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The C-CRK gene, cellular homolog of the avian v-crk oncogene, encodes two alternatively spliced adaptor signaling proteins, CRKI (28 kDa) and CRKII (40 kDa). Both CRKI and CRKII have been shown to activate kinase signaling and anchorage-independent growth in vitro and CRKI transformed cells readily form tumors in nude mice. Affymetrix oligonucleotide arrays were used to analyse 86 lung adenocarcinomas and 10 uninvolved lung tissues. C-CRK mRNA expression was increased in more advanced (stage III versus stage I), larger (T 2-4 versus T 1 ), and poorly differentiated tumors and in tumors from patients demonstrating poor survival (P ¼ 0.00034). An overlapping series of 93 lung adenocarcinomas (64 stage I and 29 stage III) and 10 uninvolved lung specimens were measured for quantitative differences in CRKI and CRKII protein levels using 2-D PAGE. CRK protein spots were identified using mass spectrometry and 2-D Western blotting. A significant increase in levels of the CRKI oncoprotein and the phosphorylated isoform of CRKII was observed in tumors (Po0.05). No difference in protein level was evident between stages. Concordant with mRNA expression, CRKI and CRKII were increased in poorly differentiated tumors (Po0.05). CRK immunohistochemical analysis of tumor tissue arrays using the same tumor series also demonstrated increased abundance of nuclear and cytoplasmic CRK in more proliferative tumors (Po0.05). This study provides the first quantitative analysis of discrete CRKI and CRKII protein isoforms in human lung tumors and provides evidence that the C-CRK proto-oncogene may foment a more aggressive phenotype in lung cancers.

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The adaptor protein Crk connects multiple cellular stimuli to the JNK signaling pathway

Cited by 168 publications

References 43 publications

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

FAK engages multiple pathways to maintain survival of fibroblasts and epithelia – differential roles for paxillin and p130Cas

Stress-induced corneal epithelial apoptosis mediated by K+ channel activation

Increased C-CRK proto-oncogene expression is associated with an aggressive phenotype in lung adenocarcinomas

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