页数：55页文件大小：1.23 MB来源： 分子生物学基因Geneppt课件
本课件为《分子生物学》第26章信号转导（Signal transduction），依据 Gene VII 教材编排，沿Carriers等小节推进，讲解本章核心概念与分子机制，配逐页图示与文字版。
Chapter 26 Signal transduction
Figure 26.1 Over view: information may be transmitted from the exterior to the interior of the cell by movement of a ligand or by signal transduction.
Figure 26.2 Three means for transfer ring material of various sizes into the cell are provided by ion channels, receptor-mediated ligand transport, and receptor internaliz at ion.
Figure 26.3 A signal may be transduced by activating the kinase activity of the cytoplasmic domain of a transmembrane receptor or by dissociating a G protein into subunits that act on target proteins on the membrane.
Figure 26.4 A carrier (porter) transports a solute into the cell by a conformational change that brings the solute-binding site from the exterior to the interior, while an ion channel is controlled by the opening of a gate (which might in principle be located on either side of the membrane).
Figure 26.4 A carrier (porter) transports a solute into the cell by a conformational change that brings the solute-binding site from the exterior to the interior, while an ion channel is controlled by the opening of a gate (which might in principle be located on either side of the membrane).
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Figure 26.5 A channel may be created by amphipathic helices, which present their hydrophobic faces to the lipid bilayer, while juxtaposing their charged faces away from the bilayer. In this example, the channel is lined with positive charges, which would encourage the passage of anions.
Figure 26.6 A potassium channel has a pore consisting of unusual transmembrane regions, with a gate whose mechanism of action resembles a ball and chain.
Figure 26.7 The pore of a potassium channel consists of three regions.
Figure 26.8 A model of the potassium channel pore shows electrostatic charge (blue = positive, white = neutral, red = negative) and hydrophobicity (= yellow). Photograph kindly provided by Rod Mac Kinnon.
Figure 26.9 The acetyl-choline receptor consists of a ring of 5 subunits, protruding into the extra-cellular space, and narrowing to form an ion channel through the membrane.
Figure 26.10 Classes of G proteins are distinguished by their effectors and are activated by a variety of transmembrane receptors.
Figure 26.11 Activation of Gs causes the a subunit to activate adenylate cyclase.
Oncogenes are genes whose products have the ability to trans form eukaryotic cells so that they grow in a manner analogous to tumor cells. Oncogenes carried by retroviruses have names of the form v-onc.
Figure 26.12 Effectors for receptor tyrosine kinases include phospholipases and kinases that act on lipids to generate second messengers.
Figure 26.13 The principle under lying signal transduction by a tyrosine kinase receptor is that ligand binding to the extracellular domain triggers dimerization; this causes a conformational change in the cytoplasmic domain that activates the tyrosine kinase catalytic activity.
Figure 26.14 Binding of ligand to the extracellular domain can induce aggreg at ion in several ways. The common feature is that this causes new contacts to form between the cytoplasmic domains.
Figure 26.15 Several types of proteins involved in signaling have SH2 and SH3 domains.
Figure 26.16 Phosphorylation of tyrosine in an SH2-binding domain creates a binding site for a protein that has an SH2 domain.
Figure 26.17 Autophosphoryl at ion of the cytosolic domain of the PDGF receptor creates SH2-binding sites for several proteins. Some sites can bind more than one type of SH2 domain. Some SH2-containing proteins can bind to more than one site. The kinase domain consists of two separated regions (shown in blue), and is activated by the phosphorylation site in it.
Figure 26.18 The crystal structure of an SH2 domain (purple strands) bound to a peptide containing phosphotyrosine shows that the P-Tyr (white) fits into the SH2 domain, and the 4 C-terminal amino acids in the peptide (backbone yellow, side chains green) also make contact. Photograph kindly provided by John Kuriyan.
Figure 26.19 Autophosphoryl at ion triggers the kinase activity of the cytoplasmic domain of a receptor. The target protein may be recognized by an SH2 domain. The signal may subsequently be passed along a cascade of kinases.
Figure 26.20 A common signal transduction cascade passes from a receptor tyrosine kinase through an adaptor to activate Ras, which triggers a series of Ser/Thr phosphorylation events. Finally, activated MAP kinases enter the nucleus and phosphorylate transcription factors. Missing components are indicated by successive arrows.
Figure 26.29 Homologous proteins are found in signal transduction cascades in a wide variety of organisms.
Figure 26.21 The Ras cascade is initiated by a series of activation events that occur on the cytoplasmic face of the plasma membrane.
Figure 26.17 Autophosphoryl at ion of the cytosolic domain of the PDGF receptor creates SH2-binding sites for several proteins. Some sites can bind more than one type of SH2 domain. Some SH2-containing proteins can bind to more than one site. The kinase domain consists of two separated regions (shown in blue), and is activated by the phosphorylation site in it.
Figure 26.22 Phosphorylation at different sites on a receptor tyrosine kinase may either activate or inactivate the signal transduction pathway.
Figure 6.37 Monomeric G proteins are active when bound to GTP and inactive when bound to GDP. Their activity is controlled by other proteins; inactivating functions are shown in blue, and activating functions are shown in red.
Figure 26.23 The relative amounts of Ras-GTP and Ras-GDP are controlled by two proteins. Ras-GAP inactivates Ras by stimulating hydrolysis of GTP. SOS (GEF) activates Ras by stimulating replacement of GDP by GTP, and is responsible for recycling of Ras after it has been inactivated.
Figure 26.24 Discrete domains of Ras proteins are responsible for guanine nucleotide binding, effector function, and membrane attachment.
Figure 26.25 The crystal structure of Ras protein has 6 b strands, 4 a helices, and 9 connecting loops. The GTP is bound by a pocket generated by loops L9, L7, L2, and L1.
Figure 26.26 Changes in cell structure that occur during growth or trans formation are mediated via monomeric G proteins.
Scaffold of a chromosome is a proteinaceous structure in the shape of a sister chromatid pair, generated when chromosomes are depleted of histones.
Figure 26.20 A common signal transduction cascade passes from a receptor tyrosine kinase through an adaptor to activate Ras, which triggers a series of Ser/Thr phosphorylation events. Finally, activated MAP kinases enter the nucleus and phosphorylate transcription factors. Missing components are indicated by successive arrows.
Figure 26.19 Autophosphoryl at ion triggers the kinase activity of the cytoplasmic domain of a receptor. The target protein may be recognized by an SH2 domain. The signal may subsequently be passed along a cascade of kinases.
Figure 26.21 The Ras cascade is initiated by a series of activation events that occur on the cytoplasmic face of the plasma membrane.
Figure 26.27 A signal transduction cascade passes to the nucleus by translocation of a component of the pathway or of a transcription factor. The factor may translocate directly as a result of phosphorylation or may be released when an inhibitor is phosphorylated.
Figure 26.28 Pathways activated by receptor tyrosine kinases and by serpentine receptors converge upon MEK.
Figure 26.29 Homologous proteins are found in signal transduction cascades in a wide variety of organisms.
Figure 26.30 STE5 provides a scaffold that is necessary for MEKK, MEK, and MAPK to assemble into an active complex.
Figure 26.31 JNK is a MAP-like kinase that can be activated by UV light or via Ras.
Figure 26.32 Three MAP kinase pathways have analogous components. Crosstalk between the pathways is shown by grey arrows.
Figure 26.33 When cyclic AMP binds to the R subunit of PKA, the C subunit is released; some C subunits diffuse to the nucleus, where they phosphorylate CREB.
Figure 26.10 Classes of G proteins are distinguished by their effectors and are activated by a variety of transmembrane receptors.
Figure 26.34 Cytokine receptors associate with and activate JAK kinases. STATs bind to the complex and are phosphorylated. They dimerize and translocate to the nucleus. The complex binds to DNA and activates transcription.
Figure 26.35 Activation of TGFb receptors causes phosphorylation of a Smad, which is imported into the nucleus to activate transcription.
Figure 26.36 Activation of a complex at the plasma membrane triggers release of a subunit that migrates to the nucleus to activate transcription.
Figure 29.31 Wg secretion is assisted by porc. Wg activates the Dfz2 receptor, which inhibits Zw3 kinase. Active Zw3 causes turn over of Arm. Inhibition of Zw3 stabilizes Arm, allowing it to translocate to the nucleus. In the nucleus, Arm partners Pan, and activates target genes (including engrailed). A similar pathway is found in vertebrate cells (components named in blue).
1.Integral proteins of the plasma membrane offer several means for communic at ion between the extracellular milieu and the cytoplasm.2.Ions may be transported by carrier proteins, which may utilize passive diffusion or may be connected to energy sources to undertake active diffusion.3.Receptors typically are group I proteins, with a single transmembrane domain, consisting exclusively of uncharged amino acids, connecting the extracellular and cytosolic domains.4.The phosphorylation creates a binding site for the SH2 motif of a target protein.
5.One group of effectors consists of enzymes that generate second messengers, most typically phospholipases and kinases that generate or phosphorylate small lipids.6.The connection from receptor tyrosine kinases to the MAP kinase pathway passes through Ras.7.An alternative connection to the MAP kinase cascade exists from serpentine receptors. 8.The cyclic AMP pathway for activating transcription proceeds by releasing the catalytic subunit of PKA in the cytosol.9.JAK-STAT pathways are activated by cytokine receptors.
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