scholarly journals MAP kinases and cell migration

2004 ◽  
Vol 117 (20) ◽  
pp. 4619-4628 ◽  
Author(s):  
C. Huang
Keyword(s):  
Cell Migration ◽  
Map Kinases

scholarly journals A cryptic tubulin-binding domain links MEKK1 to curved tubulin protomers

2020 ◽  
Vol 117 (35) ◽  
pp. 21308-21318 ◽  
Author(s):  
Pavel Filipčík ◽  
Sharissa L. Latham ◽  
Antonia L. Cadell ◽  
Catherine L. Day ◽  
David R. Croucher ◽  
...  
Keyword(s):  
Cell Migration ◽  
Map Kinases ◽  
Leading Edge ◽  
Structural Features ◽  
Selective Enrichment ◽  
Microtubule Polymerization ◽  
Binding Interface ◽  
Protein Map ◽  
Tubulin Binding ◽  
Mitogen Activated Protein

The MEKK1 protein is a pivotal kinase activator of responses to cellular stress. Activation of MEKK1 can trigger various responses, including mitogen-activated protein (MAP) kinases, NF-κB signaling, or cell migration. Notably, MEKK1 activity is triggered by microtubule-targeting chemotherapies, among other stressors. Here we show that MEKK1 contains a previously unidentified tumor overexpressed gene (TOG) domain. The MEKK1 TOG domain binds to tubulin heterodimers—a canonical function of TOG domains—but is unusual in that it appears alone rather than as part of a multi-TOG array, and has structural features distinct from previously characterized TOG domains. MEKK1 TOG demonstrates a clear preference for binding curved tubulin heterodimers, which exist in soluble tubulin and at sites of microtubule polymerization and depolymerization. Mutations disrupting tubulin binding decrease microtubule density at the leading edge of polarized cells, suggesting that tubulin binding may play a role in MEKK1 activity at the cellular periphery. We also show that MEKK1 mutations at the tubulin-binding interface of the TOG domain recur in patient-derived tumor sequences, suggesting selective enrichment of tumor cells with disrupted MEKK1–microtubule association. Together, these findings provide a direct link between the MEKK1 protein and tubulin, which is likely to be relevant to cancer cell migration and response to microtubule-modulating therapies.

scholarly journals Phosphorylation of WAVE2 by MAP kinases regulates persistent cell migration and polarity

2007 ◽  
Vol 120 (23) ◽  
pp. 4144-4154 ◽  
Author(s):  
C. M. Danson ◽  
S. M. Pocha ◽  
G. B. Bloomberg ◽  
G. O. Cory
Keyword(s):  
Cell Migration ◽  
Map Kinases ◽  
Persistent Cell

scholarly journals Regulation of Cell Contraction and Membrane Ruffling by Distinct Signals in Migratory Cells

1999 ◽  
Vol 146 (5) ◽  
pp. 1107-1116 ◽  
Author(s):  
David A. Cheresh ◽  
Jie Leng ◽  
Richard L. Klemke
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Map Kinases ◽  
Collagen Matrix ◽  
Adaptor Proteins ◽  
Cell Interaction ◽  
Cell Contraction ◽  
Rac Gtpase ◽  
Membrane Ruffling ◽  
Myosin Motors

Cell migration and wound contraction requires assembly of actin into a functional myosin motor unit capable of generating force. However, cell migration also involves formation of actin-containing membrane ruffles. Evidence is provided that actin-myosin assembly and membrane ruffling are regulated by distinct signaling pathways in the migratory cell. Interaction of cells with extracellular matrix proteins or cytokines promote cell migration through activation of the MAP kinases ERK1 and ERK2 as well as the molecular coupling of the adaptor proteins p130CAS and c-CrkII. ERK signaling is independent of CAS/Crk coupling and regulates myosin light chain phosphorylation leading to actin-myosin assembly during cell migration and cell-mediated contraction of a collagen matrix. In contrast, membrane ruffling, but not cell contraction, requires Rac GTPase activity and the formation of a CAS/Crk complex that functions in the context of the Rac activating protein DOCK180. Thus, during cell migration ERK and CAS/Crk coupling operate as components of distinct signaling pathways that control actin assembly into myosin motors and membrane ruffles, respectively.

scholarly journals A cryptic tubulin-binding domain links MEKK1 to microtubule remodelling

2020 ◽  
Author(s):  
Pavel Filipčík ◽  
Sharissa L. Latham ◽  
Antonia L. Cadell ◽  
Catherine L. Day ◽  
David R. Croucher ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Map Kinases ◽  
Leading Edge ◽  
Structural Features ◽  
Microtubule Assembly ◽  
Selective Enrichment ◽  
Binding Interface ◽  
Tubulin Binding ◽  
Microtubule Networks

ABSTRACTThe MEKK1 protein is a pivotal kinase activator of responses to cellular stress. Activation of MEKK1 can trigger various responses, including mitogen activated protein (MAP) kinases, NF-κB signalling, or cell migration. Notably, MEKK1 activity is triggered by microtubule-targeting chemotherapies, amongst other stressors. Here we show that MEKK1 contains a previously unidentified tumour overexpressed gene (TOG) domain. The MEKK1 TOG domain binds to tubulin heterodimers—a canonical function of TOG domains—but is unusual in that it appears alone rather than as part of a multi-TOG array, and has structural features distinct from previously characterised TOG domains. MEKK1 TOG demonstrates a clear preference for binding curved tubulin heterodimers, which exist in soluble tubulin and at sites of microtubule polymerisation and depolymerisation. Mutations disrupting tubulin-binding lead to destabilisation of the MEKK1 protein in cells, and ultimately a decrease in microtubule density at the leading edge of polarised cells. We also show that MEKK1 mutations at the tubulin-binding interface of the TOG domain recur in patient derived tumour sequences, suggesting selective enrichment of tumour cells with disrupted MEKK1–microtubule association. Together, these findings provide a direct link between the MEKK1 protein and tubulin, which is likely to be relevant to cancer cell migration and response to microtubule-modulating therapies.SIGNIFICANCE STATEMENTThe protein kinase MEKK1 activates stress response pathways in response to various cellular stressors, including chemotherapies that disrupt dynamics of the tubulin cytoskeleton. Filipčík et al., show that MEKK1 contains a previously uncharacterised domain that can preferentially bind to the curved tubulin heterodimer—which is found at sites of microtubule assembly and disassembly. Mutations that interfere with MEKK1-tubulin binding disrupt microtubule networks in migrating cells and are enriched in patient-derived tumour sequences. These results suggest that MEKK1-tubulin binding may be relevant to cancer progression, and the efficacy of microtubule-disrupting chemotherapies that require the activity of MEKK1.

Phospatidylinositol 3-kinase and P42/44 map kinases are involved in a novel effect of glycine-extended epithelial cell migration

2000 ◽  
Vol 94 (1-3) ◽  
pp. 54
Author(s):  
Frederic Hollande ◽  
E. Blanc ◽  
A. Choquet ◽  
D. Lee ◽  
J.-P. Bali ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Map Kinases ◽  
Epithelial Cell Migration

Neutrophil migration through in vitro interstitial matrix

1992 ◽  
Vol 50 (1) ◽  
pp. 894-895
Author(s):  
J. Roemer ◽  
S.R. Simon
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Inflammatory Cell ◽  
Neutrophil Migration ◽  
Culture Conditions ◽  
Aortic Smooth Muscle ◽  
Specific Culture

We are developing an in vitro interstitial extracellular matrix (ECM) system for study of inflammatory cell migration. Falcon brand Cyclopore membrane inserts of various pore sizes are used as a support substrate for production of ECM by R22 rat aortic smooth muscle cells. Under specific culture conditions these cells produce a highly insoluble matrix consisting of typical interstitial ECM components, i.e.: types I and III collagen, elastin, proteoglycans and fibronectin.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

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