The p38 MAP kinase signalling pathway controls inflammatory responses and is an important target of anti-inflammatory drugs. Although pro-inflammatory cytokines such as interleukin-1β (IL-1β) appear to induce only transient activation of p38 (over ∼ 60 min), longer cytokine exposure is necessary to induce p38-dependent effector genes. Here we study the dynamics of p38 activation in individual c...

Integrin activation (inside-out signaling) in platelets can be initiated by agonists such as von Willebrand factor (VWF) and thrombin. Here we show that a mitogenactivated protein kinase (MAPK), p38, plays an important role in the activation of integrin IIb 3 induced by VWF and thrombin. A dominant-negative mutant of p38, p38AF, inhibits IIb 3 activation induced by VWF binding to its receptor, ...

Integrin activation (inside-out signaling) in platelets can be initiated by agonists such as von Willebrand factor (VWF) and thrombin. Here we show that a mitogenactivated protein kinase (MAPK), p38, plays an important role in the activation of integrin IIb 3 induced by VWF and thrombin. A dominant-negative mutant of p38, p38AF, inhibits IIb 3 activation induced by VWF binding to its receptor, ...

Plasticity of the resilient keratin intermediate filament cytoskeleton is an important prerequisite for epithelial tissue homeostasis. Here, the contribution of stress-activated p38 MAPK to keratin network organization was examined in cultured cells. It was observed that phosphorylated p38 colocalized with keratin granules that were rapidly formed in response to orthovanadate. The same p38(p) r...

p38 MAP kinase (p38) and JNK have been described as playing a critical role in the response to a variety of environmental stresses and proinflammatory cytokines. It was recently reported that hematopoietic cytokines activate not only classical MAP kinases (ERK), but also p38 and JNK. However, the physiological function of these kinases in hematopoiesis remains obscure. We found that all MAP kin...

The members of the p38 subfamily of Mitogen-Activated Protein Kinases (MAPKs) are a versatile group of proteins, that function as signal transducers involved in key cellular functions. Initially, p38 MAPKs were associated with inflammatory and cellular stress responses and, as such, p38 has been an important target for anti-inflammatory therapies. Recently, increasing evidence has directly impl...

OBJECTIVES The purpose of this study was to determine whether p38 mitogen-activated protein kinase (p38-MAPK) contributes to tumor necrosis factor-alpha (TNFalpha)-induced contractile depression. BACKGROUND Tumor necrosis factor has both beneficial and detrimental consequences that may result from the activation of different downstream pathways. Tumor necrosis factor activates p38-MAPK, a str...

Trichothecene mycotoxins rapidly induce p38-mediated gene expression and apoptosis in mononuclear phagocytes via a process known as the ribotoxic stress response. We hypothesized that the trichothecene deoxynivalenol (DON) induces interaction of p38 with the ribosome. Two models, U937 human monocytes and RAW 264.7 murine macrophages, were used to test this hypothesis based on their capacity to ...

Transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) receptors were identified in human esophageal squamous epithelial cell line HET-1A by RT-PCR and by Western blot. In fura-2 AM-loaded cells, the TRPV1 agonist capsaicin caused a fourfold cytosolic calcium increase, supporting a role of TRPV1 as a capsaicin-activated cation channel. Capsaicin increased production of plate...

Hyperglycemia induces p38 MAPK-mediated renal proximal tubular cell (RPTC) apoptosis. The current study hypothesized that alteration of the Akt signaling pathway by hyperglycemia may contribute to p38 MAPK activation and development of diabetic nephropathy. Immunoblot analysis demonstrated a hyperglycemia-induced increase in Akt phosphorylation in diabetic kidneys at 1 mo, peaking at 3 mo, and ...