细胞功能测定

The Mitogen-Activated Protein Kinase (MAPK) family of signaling molecules regulates a number of cellular processes through the direct phosphorylation and regulation of a plethora of cellular proteins. Identifying the direct substrates of the MAPK pathway proteins is important ...

The mitogen-activated protein (MAP) kinases are ubiquitous intracellular signaling proteins that respond to a variety of extracellular signals and regulate most cellular functions including proliferation, apoptosis, migration, differentiation, and secretion. The fo ...

Extracellular signal-regulated kinase 5 (ERK5) is also known as big MAPK (BMK1) or MAPK7. ERK5 is 115 kDa in mass and therefore larger than the other MAPKs such as ERK1/2, JNK, and p38. Like other MAPKs, ERK5 is ubiquitously expressed in mammalian cells and is part of a three kinase cascade involving a MAPK kin ...

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cellular responses to inflammatory stimuli and environmental stresses. Extracellular stimuli activate kinases upstream of p38, such as MKK3 and MKK6, which subsequently phosphorylate p38. p38 th ...

The stress-activated protein kinase/c-jun N-terminal kinases (SAPK/JNKs) are mitogen-activated protein kinases (MAPKs) that are activated by stressful and inflammatory stimuli and regulate cellular responses such as proliferation, differentiation, and apoptosis. The ...

The ERK signaling cascade is composed of several protein kinases that sequentially activate each other by phosphorylation. This pathway is a central component of a complex signaling network that regulates important cellular processes including proliferation, differentiat ...

Sequential activation of kinases within the mitogen-activated protein (MAP) kinase (MAPK) cascades is a common, and evolutionary-conserved mechanism of signal transduction. Four MAPK cascades have been identified in the last 20 years and those are usually named according to the MAPK c ...

Accumulating evidence indicates that p44ERK1 and p42ERK2 mitogen-activated protein kinases (MAPKs) have distinct quantitative roles in cell signaling. In our recently proposed model of regulation of ERK1 and ERK2, p42 plays a major role in delivering signals from the cell membrane to t ...

Proteomics refers to the analysis of expression, localization, functions, posttranslational modifications, and interactions of proteins expressed by a genome at a specific condition and at a specific time. Mass spectrometry (MS)-based proteomic methods have emerged as a key tech ...

In Drosophila, like in other metazoans, receptor tyrosine kinase (RTK) signaling pathways control diverse cellular processes such as migration, growth, fate determination, and differentiation (Shilo, Development 132:4017–4027, 2005). Activation of RTKs by their extracellu ...

Mitogen-activated protein (MAP) kinases play central roles in transmitting extracellular and intracellular information in a wide variety of situations in eukaryotic cells. Their activities are perturbed in a large number of diseases, and their activating kinases are currently t ...

In this chapter, we describe general methods used to create dynamic computational models of kinase signalling cascades, and tools to support this activity. We focus on the ordinary differential equation models, and show how these fit into a general framework of qualitative and quantitati ...

The convergence and coordinated cross talk of different signalling pathways forms a regulatory network which determines the biological outcome to environmental cues. The MAPK pathways are one of the important routes by which extracellular signals are transduced into intracell ...

Signals transmitted by ERK MAP Kinases regulate the functions of multiple substrates present in the nucleus and the cytoplasm. Once phosphorylated, ERKs dimerize. The functions of these dimers had remained elusive until recently when we demonstrated that ERK dimers are assembled usi ...

ERK cascade scaffolds serve as docking platforms to coordinate the assembly of multiprotein complexes that contribute to the spatial and temporal control of ERK signaling. Given that protein–protein interactions are essential for scaffold function, determining the full reper ...

Signaling through MAPK pathways involves a network of activating kinases and inactivating phosphatases. While single MAPK kinases account for specific activation of the distinct MAPKs, inactivation of MAPKs by phosphatases involves a wider spectrum of enzymes, with phosphata ...

The action of ERK1 and ERK2 activity on the nuclear substrates requires crossing the nuclear envelope and the localization of phospho-ERK into the nucleus. The nucleo-cytoplasmic trafficking of ERK is therefore crucial for the correct functioning of the pathway. Indeed, this step is nece ...

The nuclear–cytoplasmic distribution of ERK2 is regulated in response to various stimuli and changes in cell context. Furthermore, the nuclear flux of ERK2 occurs by several energy- and carrier-dependent and -independent mechanisms. ERK2 has been shown to translocate into and out of the n ...

Mitogen-activated protein (MAP) kinases are a large family of enzymes composed of about four subfamilies, each containing several isoforms and splicing variants. Many MAP kinases are coexpressed in each eukaryotic cell and coactivated in response to various stimuli. It is, therefore, ...

Hydrogen exchange mass spectrometry (HX-MS) is an experimental technique that can be used to �examine solvent accessibility and conformational mobility in biological macromolecules. This chapter summarizes studies using HX-MS to examine the regulation of conformation, pro ...