Pancreatic Tumor Cells with Mutant K-ras Suppress ERK Activity by MEK-Dependent Induction of MAP Kinase Phosphatase-2

2001 ◽  
Vol 280 (4) ◽  
pp. 992-997 ◽  
Author(s):  
Michele T. Yip-Schneider ◽  
Amy Lin ◽  
Mark S. Marshall
Keyword(s):  
Map Kinase ◽  
Tumor Cells ◽  
Pancreatic Tumor ◽  
Map Kinase Phosphatase ◽  
Erk Activity

ACTIVATION OF PAR1 AND PAR2 RESULTS IN CALCIUM AND MAP KINASE DEPENDENT PROLIFERATION OF PANCREATIC TUMOR CELLS

Pancreas ◽  
2005 ◽  
Vol 31 (4) ◽  
pp. 457
Author(s):  
M Morris ◽  
P A Phillips ◽  
R Sharif ◽  
S Ghaffoor ◽  
R Dawra ◽  
...  
Keyword(s):  
Map Kinase ◽  
Tumor Cells ◽  
Pancreatic Tumor

scholarly journals Integrin-Associated Protein Stimulates α2β1-Dependent Chemotaxis via GI-Mediated Inhibition of Adenylate Cyclase and Extracellular-Regulated Kinases

1999 ◽  
Vol 147 (2) ◽  
pp. 389-400 ◽  
Author(s):  
Xue-Qing Wang ◽  
Frederik P. Lindberg ◽  
William A. Frazier
Keyword(s):  
Map Kinase ◽  
Pertussis Toxin ◽  
Mek Inhibitor ◽  
Inhibitory Input ◽  
Soluble Collagen ◽  
Map Kinase Phosphatase ◽  
Mitogen Activated Protein ◽  
Extracellular Regulated Kinase ◽  
Erk Activity ◽  
Α2β1 Integrin

Integrin-associated protein (IAP/CD47) augments the function of α2β1 integrin in smooth muscle cells (SMC), resulting in enhanced chemotaxis toward soluble collagen (Wang, X-Q., and W.A. Frazier. 1998. Mol. Biol. Cell. 9:865). IAP-deficient SMC derived from IAP−/− animals did not migrate in response to 4N1K (KRFYVVMWKK), a peptide agonist of IAP derived from the COOH-terminal domain of thrombospondin-1 (TSP1). When normal SMC were preincubated with 4N1K or an anti-α2β1 function-stimulating antibody, cell migration to soluble collagen was significantly enhanced. 4N1K-induced chemotaxis was blocked by treatment of SMC with pertussis toxin indicating that IAP acts through Gi. In agreement with this, 4N1K evoked a rapid decrease in cAMP levels which was intensified in the presence of collagen, and forskolin and 8-Br-cAMP both inhibited SMC migration stimulated via IAP. 4N1K strongly inhibited extracellular regulated kinase (ERK) activation in SMC attaching to collagen and reduced basal ERK activity in suspended SMC. Pertussis toxin treatment of SMC significantly activated ERK, suggesting that an inhibitory input was alleviated. Inhibition of ERK activity by (a) the MAP kinase kinase (MEK) inhibitor, PD98059, (b) antisense oligonucleotide depletion of ERK, and (c) expression of mitogen-activated protein (MAP) kinase phosphatase-1 in SMC all led to increased migration to collagen, 4N1K, or 4N1K plus collagen. Thus, IAP stimulates α2β1 integrin-mediated SMC migration via Gi-mediated inhibition of ERK activity and suppression of cyclic AMP levels. Both of these signaling pathways could directly modulate the state of the integrin as well as impact downstream components of the cell motility apparatus.

scholarly journals MAP Kinase Phosphatase-1 Gene Transcription in Rat Neuroendocrine Cells Is Modulated by a Calcium-sensitive Block to Elongation in the First Exon

2001 ◽  
Vol 276 (36) ◽  
pp. 33319-33327 ◽  
Author(s):  
Stephan Ryser ◽  
Silvia Tortola ◽  
Goedele van Haasteren ◽  
Marco Muda ◽  
Senlin Li ◽  
...  
Keyword(s):  
Map Kinase ◽  
Gene Transcription ◽  
Neuroendocrine Cells ◽  
Map Kinase Phosphatase

scholarly journals MAP Kinase Phosphatase 1 (MKP-1/DUSP1) Is Neuroprotective in Huntington's Disease via Additive Effects of JNK and p38 Inhibition

2013 ◽  
Vol 33 (6) ◽  
pp. 2313-2325 ◽  
Author(s):  
D. M. Taylor ◽  
R. Moser ◽  
E. Regulier ◽  
L. Breuillaud ◽  
M. Dixon ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Map Kinase ◽  
Huntington’S Disease ◽  
Additive Effects ◽  
Map Kinase Phosphatase

scholarly journals Pancreatic tumor cell metastasis is restricted by MT1-MMP binding protein MTCBP-1

2018 ◽  
Vol 218 (1) ◽  
pp. 317-332 ◽  
Author(s):  
Li Qiang ◽  
Hong Cao ◽  
Jing Chen ◽  
Shaun G. Weller ◽  
Eugene W. Krueger ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Pancreatic Tumor ◽  
Binding Protein ◽  
Critical Role ◽  
Inverse Correlation ◽  
Pancreatic Tumors ◽  
Matrix Remodeling ◽  
Peripheral Tissues

The process by which tumor cells mechanically invade through surrounding stroma into peripheral tissues is an essential component of metastatic dissemination. The directed recruitment of the metalloproteinase MT1-MMP to invadopodia plays a critical role in this invasive process. Here, we provide mechanistic insight into MT1-MMP cytoplasmic tail binding protein 1 (MTCBP-1) with respect to invadopodia formation, matrix remodeling, and invasion by pancreatic tumor cells. MTCBP-1 localizes to invadopodia and interacts with MT1-MMP. We find that this interaction displaces MT1-MMP from invadopodia, thereby attenuating their number and function and reducing the capacity of tumor cells to degrade matrix. Further, we observe an inverse correlation between MTCBP-1 and MT1-MMP expression both in cultured cell lines and human pancreatic tumors. Consistently, MTCBP-1–expressing cells show decreased ability to invade in vitro and metastasize in vivo. These findings implicate MTCBP-1 as an inhibitor of the metastatic process.

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