细胞信号通路(Cell Signaling)

• Errors in cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes.
• By understanding cell signalling, diseases may be treated effectively and, theoretically, artificial tissues may be created.
• G protein-coupled receptors are involved in many diseases, and are also the target of around half of all modern medicinal drugs.
• There are two principal signal transduction pathways involving the G-protein coupled receptors: cAMP signal pathway and Phosphatidylinositol signal pathway.
Signaling Receptor
• A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule.
• The response of a particular cell to a signal depends on the type of proteins it contains.
G-protein-coupled receptors
G protein-coupled receptors are integral membrane proteins that possess seven membrane-spanning domains or transmembrane helices.
• For example, after the epidermal growth factor (EGF) receptor binds with its ligand EGF, two receptors dimerize and then undergo phosphorylation of the tyrosine residues in the enzyme portion of each receptor molecule, which will activate the tyrosine protein kinase and catalyze further intracellular reactions.
Cell Receptors
Cell surface receptors
• Cell surface receptors (membrane receptors, transmembrane receptors) are specialized integral membrane proteins that take part in communication between the cell and the outside world. •
An example of this are immune cells.
Juxtacrine signals target adjacent (touching) cells. These signals are transmitted along cell membranes via protein or lipid components integral to the membrane and are capable of affecting either the emitting cell or cells immediately adjacent.
Cell surface receptors
• Extracellular signaling molecules (usually hormones, neurotransmitters, cytokines, growth factors or cell recognition molecules) attach to the receptor, triggering changes in the function of the cell.
• Receptor tyrosine kinases is the one kind with the largest population and most widely application. The majority of these molecules are receptors for growth factors and hormones like epidermal growth factor (EGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), insulin, nerve growth factor (NGF) etc. • Most of these receptors will dimerize after binding with their ligands in order to activate further signal transductions.
Neurotransmitters represent an example.
Autocrine signals are produced by the target cell, are secreted, and effect the target cell itself via receptors. Sometimes autocrine cells can target cells close by if they are the same type of cell as the emitting cell.
Responding to the outside world
Extracellular signal → receptor → transducer → effector
Forms of signaling molecules
Gasses
• • • • • • • NO CO Testosterone Eswk.baidu.comradiol Progesterone Glucocorticoids
Cell Signaling
• Cell signalling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. • The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue homeostasis.
• Calcium is used in many processes including muscle contraction, neurotransmitter release from nerve endings, and cell migration.
Enzyme-linked Cell Surface Receptors
• G protein-coupled receptors comprise a large family transmembrane receptors. • They are found only in eukaryotes. • The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins.
• Signal transduction occurs when an extracellular signaling molecule activates a specific receptor located on the cell surface or inside the cell.
• In turn, this receptor triggers a biochemical chain of events inside the cell, creating a response. Depending on the cell, the response alters the cell's metabolism, shape, gene expression, or ability to divide.
Endocrine cells produce hormones that travel through the blood to reach all parts of the body.
Pararine signals target cells in the vicinity of the emitting cell.
• Enzyme-linked receptors are either enzymes themselves, or are directly associated with the enzymes that they activate. • These are usually single-pass transmembrane receptors, with the enzymatic portion of the receptor being intracellular. The majority of enzyme-linked receptors are protein kinases, or associate with protein kinases.
Ion channel-linked receptor
Ion-channels (including cation-channels and anion-channels) themselves and constitute a large family of multipass transmembrane proteins. They are involved in rapid signaling events most generally found in electrically excitable cells such as neurons. Opening and closing of Ion channels are controlled by neurotransmitters.
– Cortisol
Steroid Hormones
Mineralocorticoids
– Aldosterone
Forms of signaling molecules
• Neurotransmitters
Multiple levels of cell signaling
Endocrine signals target distant cells.