D. Transport processes within an eukaryotic cell 3. Active transport: Carrier protein-mediated movement up the gradient B. Cells carry out active transport in three main ways C. Direct active transport depends on four types of transport ATPases 4. Indirect active transport is driven by Ion gradients ----- Cotransport The difference between animal and plant cells to absorb nutrients B. Cotransport: Symport and antiport 5. Endocytosis:  Large molecules enter into cells A. Endocytosis imports extracellular molecules dissolved or suspended in fluid by forming vesicles from the plasma membrane B. Phagocytosis: The uptake of large particles C. Receptor-mediated endocytosis Chapter 5 B. Cell Signaling 1. Overview of cell signaling A. Some of the basic characteristics of cell signaling B. The forms of cell communication----- Different types of chemical signals can be received by cells C. Signal Molecules and Receptors Receptors include three classes: glycoproteins D. Two types of intracellular signaling proteins that act as Molecular Switches 2. Signal transdution mediated by  the receptors within cells A. Some small hydrophobic hormones (steroid hormones) whose receprors are intracellular gene regulatory proteins. B. Nitric oxide couples G protein-linked receptor stimulation in endothelial cells to relaxation of smooth muscle cells in blood vessels The action of Nitric oxide on blood vessels The mechanism by which acetylcholine stimulation of the endothelial cells leads to smooth muscle relaxation also explains the mechanism of action of the chemical nitroglycerin. The drug sildenafil, sold under the trade name Viagra, is an inhibitor of a cyclic GMP-specific phosphodiesterase that normally catalyzes the breakdown of cyclic GMP. 3. Signal transduction mediated by  the receptors on the cell surface A. Mediated by the Ion-Linked Receptors which convert chemical signals into electrical ones B. Signal transduction mediated by G protein-linked receptors The structure of G protein-linked receptors: Seven-helix transmembrane; C-terminal: Ser- and Thr-rich ---the sites of phosphorylation make for the desensitization of GPLR. C. Cyclic AMP signaling pathway The activation of protein kinase A by cyclic AMPs The mechanisms that shut off a signal are as important as the mechanisms that turn it on. D. The pathway through phospholipase C results in a rise in intracellular Ca+ IP3-Ca2+ pathway and DG-PKC pathway E. Receptor tyrosine kinase (RTK) and  RTK-Ras signaling pathway RTK are the second major type of cell-surface receptors Ligand binding leads to autophosphorylation of RTK MAP-kinase serine/threonine phosphorylation Pathway activated by Ras 5. Convergence, divergence, and crosstalk among different signaling pathway A. Convergence: Signals from a variety of unrelated receptors can converge to activate a common effector. B. Divergence: Signals from the same ligand can diverge to activate a variety of different effectors. C. Crosstalk: Signals can be passed back and forth between different pathways 6. In actual fact, signaling pathways in the cell are much more complex. Double Messenger system Figure 15-32 Two intracellular pathways by which activated C-kinase can activate the transcription of specific genes. In one (red arrows) C-kinase activates a phosphorylation cascade that leads to the phosphorylation of a pivotal protein kinase called MAP-kinase, which in turn phosphorylates and activates the gene regulatory protein Elk-1. Elk-1 is bound to a short DNA sequence in association with another DNA-binding protein. In the other pathway (green arrows) C-kinase activation leads to the phosphorylation of Ik-B, which releases the gene regulatory protein NF-kB so that it can migrate into the nucleus and activate the transcription of specific genes. Cholera is caused by a bacterium that multiplies in the intestine, where it produces a protein called cholera toxin. This enters the cells lining the intestine and modifies the αsubunit of G protein so that it can no longer hydrolyze its bound GTP. The altered αsubunit thus remains in the active state indefinitely, continuing to transmit a signal to its target proteins: Outflow of Na+ and water into the gut. Cytolasmic calcium levels are determined by events within a membrane. Elevation of cytosolic Ca2+ via the IP signaling pathway Signals GPLR GP PLC IP3 and DAG (twin signals). IP3 IP3 receptor(Ca2+ channel, located at the surface of sER) Elevation of cytosolic Ca2+; DAG activates PKC to phosphoralate Ser and Thr on target proteins. Calcium binds to calcium-binding proteins(CaM) which affects other proteins. Structure of calmodulin, a cytosolic protein of 148 amino acids that bind Ca2+ ions Regulating calcium concentrations in plant cells Cytosolic calcium changes in response to several stimuli, including light, pressure, gravity, and hormones. Calcium signaling aids in decreasing turgor pressure in guard cells. Ca2+/CaM dep. protein kinase (CaM-kinase) mediate many of the actions of Ca2+ in animal cells. The functions of increase the levels of cytosolic calcium-CaM : start-up embryo development after the fecundation. excitating contract of muscle cells; excitating secretion of endocrine and nerve cells. G-protein-linked receptor desensitization depends on receptor phosphorylation by PKA, PKC, CaMK2 or G-protein-linked receptor kinases(GRKs) The target cells can become desensitized to a signal molecule by five ways. Three general ways of the desensitization: 1. Receptor inactivation by alteration; 2. Receptor sequestration by internalization; 3. Receptor down-regulation by destroying in Ls. Sequestration; down-regulation; inactivation; inactivation; inhibitory protein Signaling ligands of RTKs: 1.Nerve growth factor (NGF) 2.Platelet-derived growth factor (PDGF) 3.Fibroblast growth factor (FGF) 4.Epidermal growth factor (EGF) 5.insulin and insulin-like GF(IGF-1) 6.ephrins(Eph) 7.vascular endothelial factor(VEGF) Six classes of enzyme-linked receptors have thus far been identified: Receptor tyrosine kinase(RTK); Tyrosine-kinase-associated receptor; Receptorlike tyrosine phosphatases; Receptor serine/threonine kinase; Receptor guanylyl cyclases; Histidine-kinase-associated receptor Figure 15-47 Six subfamilies of receptor tyrosine kinases. Only one or two members of each subfamily are indicated. Note that the tyrosine kinase domain is interrupted by a "kinase insert region" in some of the subfamilies. The functional significance of the cysteine-rich and immunoglobulinlike domains is unknown. RTK activity stimulated by cross-phosphorylation. Phsphorylated Tyrosine Serve as docking sites for protein with SH2 domains (Src homology region). Other protein modules such as SH3 binds to proline-rich motifs in intracellular proteins. dimerization Steps in activation of Ras by RTKs Phosphotyrosines of RTK act as binding sites for a specific SH2 protein called GRB2 (Growth factor receptor binding protein in mammalian). GRB2 is not a protein with catalytic activity, but one that functions solely as an adapter molecule that links other proteins into a complex. Sos(son of sevenless) is a guanine nucleotide exchange factor for Ras (Ras-GEF) When a ligand binds to the RTK and recruits the Grb2-Sos to the inner surface of the membrane, the Sos protein binds to Ras causing GDP/GTP exchange, thus activating Ras. In the cell, Ras activity is regulated by GAPs( GTPase –Activating proteins)—100 000-fold Ras-activated phosphorylation cascade MAP kinase=mitogen-activated protein kinase; MAP-KKK=Raf (Ser/Thr-PK) RTK-Ras signaling pathway F. Jak-STAT signaling pathway Janus kinases (Jaks) and STATs : Jaks: A class of cytoplasmic tyrosine kinases, including Jak1, Jak2, Jak3, and Tyk2, and each is associated with particular cytokine receptors; STATs: Jaks then phosphorylate and activate a set of latent gene regulatory proteins called STATs(signal transducers and activators of transcription,which have an SH2 domain),which move into the nucleus and stimulate the transcription of specific genes. Signaling ligands and Cytokine receptors: Ligands: more than 30 cytokines and hormones activate the Jak-STAT pathway by binding to cytokine