BSCI105 – SESSION 2- Tyrosine kinase receptorso Phosphorylation of target proteins- RTK Signaling Pathways (cascades)o Relay proteins are intermediates in signal transduction pathwayo Signaling cascade includes a series of relay proteins leading to indirectactivation of the ultimate target proteino Many relay molecules are protein kinases ATP used to phosphorylate targets- Phosphorylation cascadeo Phosphorylation = activation- Phosphorylationo Addition of a phosphate group to amino acids in proteins Serine, threonine, tyrosine Kinases catalyze this reactiono Removal of a phosphate group from amino acids in proteins Phosphates catalyze this reaction- Dephosphorylation- Elaborate pathwayso Amplification of signal Leads to amplification of responseo Increases specificity of responseo Potential for plasticity of response- 3 major receptor groups = G-protein coupled receptors, receptor tyrosine kinases, and the nuclear receptors- Nuclear receptorso No association with membraneo Exist in the cytoplasmo Steroid hormone receptors Intracellular receptors INACTIVE – in cytoplasm ACTIVE – bind steroid hormones Active ligand/receptor complexes move into nucleus Potent Transcription Factors – activate or repress gene expressiono Nuclear hormone receptors are great examples of signal transduction molecules – FALSE- Multicellularityo Challenges of being multicellular: Coordination of cellular processes (cell division, metabolism) Distribution of nutrients Developmental patterning Cell differentiation- Cellular communicationo Chemical signaling Act at a distance (endocrine signaling)- Hormones, growth factors Act locally (paracrine or autocrine)- Morphogens, growth factors, cytokineso Cellular signaling Neurons Synaptic signaling – nerve networks Neuroendocrine signaling- Regulate secretion by endocrine cellso Responses to signaling Same signal has multiple meanings Cells express different “downstream” signal effectors Allows one signal to coordinate a complex set of responses- Clicker: Hormones can be lipids or proteins- Hormoneso Endocrine signals Steroids Peptides Amineso Regulate/coordinate systemic processes Metabolism Reproductive physiology Behavior Rhythmic processes- Insulino Principal regulator of glucose metabolism Peptide hormone- Quaternary structure (alpha+beta peptides) Insulin receptor- Receptor tyrosine kinase Insulin release- Pancreas, islet cells Responds to glucose levels in circulation- Eat= increased blood glucose- Appropriate response = make glycogeno Diabetes caused by failure in the regulation of blood glucose by insulin Type 1—insufficient insulin production- Treated by synthetic insulin injection Type 2—insulin insensitivity (90%)- Excessive dietary glucoseo Desensitization to insulin receptorso Downregulation of insulin receptors- Growth factorso Regulate/coordinate cell division and differentiation Body/organ size Body fat Wound healing Skeletal growth Hair growth- Cytokineso Regulate division, behavior, and gene expression of blood cellso Important for immune stimulationo Interferons Released by white blood cells in response to pathogens- Morphogenso Coordinate differentiation of different cell types along a gradiento Anterior – posterioro Dorsal – ventralo Neutral – ectodermal - Developmental regulationo Coordinated growth Cell production Organ size Growth factors -- promote cell division and cell survivalo Cell differentiation Sequential – proper time Spatial – proper place- Morphogens10/11/10- Hormones regulate cellular and physiological processes- Feedback regulation: future levels of a substance are in part controlled by current levels of that substanceo Positive feedback – encourages moreo Negative feedback – already has enough- Antagonistic pathways: Opposing pathways react differently to the same stimuluso Levels controlled by sum of opposing pathwayso Goal = homeostasis - Cell division: production of new cells from existing cellso One cell grows and divides into 2 daughter cells - Prokaryoteso Single circular piece of DNA – 500x longer than cello Some evidence that the replicating chromosome is actively partitioned to each side of the growing cello Binary fission- Eukaryotic cell divisiono Cytoplasmic division (cytokinesis)o Nuclear division (mitosis, meiosis)- Reasons for cell division:o Growtho Repairo Maintenance/renewal- Cell division:o Mitosis: separation of chromosomes into daughter cells Chromatid = 1 strand of DNA When copy is made, centromere becomes bigger. During mitosis, centromere split in half. # of centromeres = # of chromosomes o Cytokinesis: physical division of cell membrane and contentso Mitosis: cell division results in 2 genetically identical daughter cells Equal cell division – daughter cells are the same Unequal cell division – daughter cells are different- The Cell Cycle:o Interphase = time not dividing (includes G1, S PHASE, G2) G1 (G0) – 1 chromatid per chromosome S phase – making more DNA (DNA synthesis) G2 – every chromosome has 2 chromatids (2 sister chromatids)- Paired chromatins = ready to divide through mytosis- Phases of Mitosis:o Prophase Chromosomes condense Nucleoli disappear Centrioles (asters) separate Mitotic spindle formso Prometaphase Transition stage Nuclear envelope disappears Kinetichores attach chromatids to spindle Spindle maturationo Metaphase Chromosomes align at metaphase plate Chromatids oriented towards poleso Anaphase Sister chromatids separate Chromatids move to poles Cell elongates along spindle axiso Teleophase/cytokinesis Two daughter nuclei form Chromosomes decondense Cell membranes partition cytoplasm into 2 daughter cellso Interphase, again (repeat)- The Mitotic Spindleo Spindle apparatus Provides scaffold and force for chromatid separation Animals have centrosomes at the poles Asters – radical elements project from centrosomes or MTOC at poles Spindle fibers – microtubule bundles Attach to chromatids at kinetochores 10/13/10CELL CYCLE REGULATION- Cytoplasmic determinants- Factors regulating cell cycle- Checkpointso Cell cycle stops at specific pointso Cytoplasmic determinants are permissive signals that allow the cycle to proceed if certain conditions are meto G1, G2, M checkpoints- G1 Checkpointo Proceed with cell cycle?o G0 –
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