BSCI105 – SESSION 2● Tyrosine kinase receptors○ Phosphorylation of target proteins● RTK Signaling Pathways (cascades)○ Relay proteins are intermediates in signal transduction pathway○ Signaling cascade includes a series of relay proteins leading to indirect activation of the ultimate target protein○ Many relay molecules are protein kinases■ ATP used to phosphorylate targets● Phosphorylation cascade○ Phosphorylation = activation● Phosphorylation○ Addition of a phosphate group to amino acids in proteins■ Serine, threonine, tyrosine■ Kinases catalyze this reaction○ Removal of a phosphate group from amino acids in proteins■ Phosphates catalyze this reaction● Dephosphorylation● Elaborate pathways○ Amplification of signal■ Leads to amplification of response○ Increases specificity of response○ Potential for plasticity of response● 3 major receptor groups = G-protein coupled receptors, receptor tyrosine kinases, and the nuclear receptors● Nuclear receptors○ No association with membrane○ Exist in the cytoplasm○ 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 expression○ Nuclear hormone receptors are great examples of signal transduction molecules – FALSE● Multicellularity○ Challenges of being multicellular:■ Coordination of cellular processes (cell division, metabolism)■ Distribution of nutrients■ Developmental patterning■ Cell differentiation● Cellular communication○ Chemical signaling■ Act at a distance (endocrine signaling)● Hormones, growth factors■ Act locally (paracrine or autocrine)● Morphogens, growth factors, cytokines○ Cellular signaling■ Neurons■ Synaptic signaling – nerve networks■ Neuroendocrine signaling● Regulate secretion by endocrine cells○ 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● Hormones○ Endocrine signals■ Steroids■ Peptides■ Amines○ Regulate/coordinate systemic processes■ Metabolism■ Reproductive physiology■ Behavior■ Rhythmic processes● Insulin○ 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 glycogen○ 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 glucose○ Desensitization to insulin receptors○ Downregulation of insulin receptors● Growth factors○ Regulate/coordinate cell division and differentiation■ Body/organ size■ Body fat■ Wound healing■ Skeletal growth■ Hair growth● Cytokines○ Regulate division, behavior, and gene expression of blood cells○ Important for immune stimulation○ Interferons■ Released by white blood cells in response to pathogens● Morphogens○ Coordinate differentiation of different cell types along a gradient○ Anterior – posterior○ Dorsal – ventral○ Neutral – ectodermal ● Developmental regulation○ Coordinated growth■ Cell production■ Organ size■ Growth factors -- promote cell division and cell survival○ 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 substance○ Positive feedback – encourages more○ Negative feedback – already has enough● Antagonistic pathways: Opposing pathways react differently to the same stimulus○ Levels controlled by sum of opposing pathways○ Goal = homeostasis ● Cell division: production of new cells from existing cells○ One cell grows and divides into 2 daughter cells ● Prokaryotes○ Single circular piece of DNA – 500x longer than cell○ Some evidence that the replicating chromosome is actively partitioned to each side of the growing cell○ Binary fission● Eukaryotic cell division○ Cytoplasmic division (cytokinesis)○ Nuclear division (mitosis, meiosis)● Reasons for cell division:○ Growth○ Repair○ Maintenance/renewal● Cell division:○ 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 ○ Cytokinesis: physical division of cell membrane and contents○ 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:○ 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:○ Prophase■ Chromosomes condense■ Nucleoli disappear■ Centrioles (asters) separate■ Mitotic spindle forms○ Prometaphase■ Transition stage■ Nuclear envelope disappears■ Kinetichores attach chromatids to spindle■ Spindle maturation○ Metaphase■ Chromosomes align at metaphase plate■ Chromatids oriented towards poles○ Anaphase■ Sister chromatids separate■ Chromatids move to poles■ Cell elongates along spindle axis○ Teleophase/cytokinesis■ Two daughter nuclei form■ Chromosomes decondense■ Cell membranes partition cytoplasm into 2 daughter cells ○ Interphase, again (repeat)● The Mitotic Spindle○ 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 kinetochores10/13/10CELL CYCLE REGULATION● Cytoplasmic determinants● Factors regulating cell cycle● Checkpoints○ Cell cycle
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