scholarly journals Molecular alterations of Ras-Raf-mitogen-activated protein kinase and phosphatidylinositol 3-kinase-Akt signaling pathways in colorectal cancers from a tertiary hospital at Kuala Lumpur, Malaysia

Apmis ◽  
2013 ◽  
Vol 121 (10) ◽  
pp. 954-966 ◽  
Author(s):  
Wai Kien Yip ◽  
Chee Wei Choo ◽  
Vincent Ching-Shian Leong ◽  
Pooi Pooi Leong ◽  
Mohd Faisal Jabar ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Tertiary Hospital ◽  
Akt Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Colorectal Cancers ◽  
Kuala Lumpur ◽  
Phosphatidylinositol 3 Kinase ◽  
Molecular Alterations ◽  
Mitogen Activated Protein

Nerve growth factor functions as a chemoattractant for mast cells through both mitogen-activated protein kinase and phosphatidylinositol 3-kinase signaling pathways

Blood ◽  
2000 ◽  
Vol 95 (6) ◽  
pp. 2052-2058 ◽  
Author(s):  
Junko Sawada ◽  
Atsuko Itakura ◽  
Akane Tanaka ◽  
Tohru Furusaka ◽  
Hiroshi Matsuda
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Mast Cells ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Mitogen Activated Protein Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Directional Migration ◽  
Nerve Growth ◽  
Mitogen Activated Protein

Abstract Despite being a well-characterized neurotrophic factor, nerve growth factor (NGF) influences survival, differentiation, and functions of mast cells. We investigated whether NGF was able to induce directional migration of rat peritoneal mast cells (PMCs). NGF clearly induced chemotactic movement of PMCs in a dose-dependent manner with the drastic morphological change and distribution of F-actin, which was completely blocked by pretreatment with Clostridium botulinumC2 toxin, an actin-polymerization inhibitor. Because PMCs constitutively express the NGF high-affinity receptor (TrkA) with a tyrosine kinase domain, we focused on downstream effectors in signaling cascades following the TrkA. NGF rapidly activated both mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K), and the addition of inhibitors specific for MAPK kinase and PI3K suppressed cell migration and these signals. In the coculture system with PMCs and fibroblasts, which produce biologically active NGF, directional migration of PMCs to fibroblasts was observed, and the addition of anti-NGF polyclonal antibodies significantly suppressed the migration of PMCs. These findings suggested that NGF initiated chemotactic movement of PMCs through both MAPK and PI3K signaling pathways following TrkA activation. Thus, locally produced NGF may play an important role in mast cell accumulation in allergic and nonallergic inflammatory conditions.

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