Cell Signaling - University of Guadalajara

WE MAKE DOCTORS Cell Signaling Cabrera Salaiza  SESSION OBJECTIVES 1. CELL SIGNALING (CELL-TO-CELL COMMUNICATION) a. Outline the G-Protein Signaling process b. Describe the Catalytic Receptor Signaling process c. Summarize the Steroid Receptor Signaling process Bibliography...

WE MAKE DOCTORS Cell Signaling Cabrera Salaiza  SESSION OBJECTIVES 1. CELL SIGNALING (CELL-TO-CELL COMMUNICATION) a. Outline the G-Protein Signaling process b. Describe the Catalytic Receptor Signaling process c. Summarize the Steroid Receptor Signaling process Bibliography: Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. 2  G-protein / catalytic receptor / steroid hormone signaling to some extent all involve phosphorylation of amino acid residues within cell via protein kinase. Common Hormones, growth factors, neurotransmitters, cytokines. ground. Serine or threonine P+ results in long lasting celular activation. Tyrosine P+ is usually a rapid cellular response. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library Signal trandsuction Autocrine signaling. An activated T lymphocyte secretes a growth factor that binds to its own receptors, promoting an immune response to a specific antigen. Paracrine signaling i.e. release of inflammatory mediators (eg, histamine) from cells that act on nearby blood vessels. The mediators cause vasodilation to increase the delivery of immune cells to the region. Endocrine signaling i.e. Thyroid hormone produced at follicles, travels through bloodstream and reaches target action site.  G-Protein Signaling Two families: Heterotrimeric G proteins / RAS superfamily. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library  From: 17 G-Protein Signaling Lippincott® Illustrated Reviews: Cell and Molecular Biology, 3e, 2024 When the human genome was Phospholipase C sequenced, it revealed that humans have about 800 Adenylyl cyclase different G-protein-coupled receptors, including many whose function is still not understood. Mitogenic Activated protein kinase Inositol 3 Phosphate https://med.stanford.edu/new Diacylglycerol s/all-news/2012/10/nobel- Ca+ prize-work-on-g-protein- coupled-receptors-paves- way-for-drug-discoveries.html Legend: Overview of G-protein signaling. Copyright © Wolters Kluwer The Ras Family From: 17 G-Protein Signaling Lippincott® Illustrated Reviews: Cell and Molecular Biology, 3e, 2024 Legend: Overview of G-protein signaling. Copyright © Wolters Kluwer Clinical Application: Pharmaceutical agents Examples of drugs targeting G-PCRs include histamine receptor blockers, opioid agonists, β-blockers and angiotensin receptor blockers.  Clinical Application Wong, TS., Li, G., Li, S. et al. G protein- coupled receptors in neurodegenerative diseases and psychiatric disorders. Sig Transduct Target Ther 8, 177 (2023). https://doi.org/10.1038/s41392-023-01427- 2  Catalytic Receptor Signaling Receptor structure. Adaptor proteins: variable. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library  Ras, STATs, gene transcription processes. PI3 – Cell growth and surival. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library Signaling via Nonreceptor Tyrosine Kinases Src family – lymphocite communication JAKs Janus Kinases – nuclear processes Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library Clinical Application: When did insulin resistance appear? Steroid Receptor Signaling Hallmark of steroid hormone signaling. Directly binding to their ligand-activated transcription factors, immediately initiate DNA transcription, thus protein synthesis.  Cholesterol. Common precursor. Hormonal production is balanced and regulated by feedback. Synthesis occurs in major organs, adrenal cortex, ovaries, testes, then transported into the bloodstream into target organs. Aldosterone: distal tubules and collecting ducts of the nephron. Progesterone: produced during ovulation and pregnancy dependent. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library  Nuclear-Steroid Signal First, bind to the intracellular receptor, this enables hormonal transportation to nucleus. Hormone reaches target site: HRE hormone response element (a protein found in cytoplasm). Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library  Type I receptors: directly stimulate HRE. Each hormone stimulates a specific HRE. Upregulation or Downregulation. Type II: must release corepressor proteins. Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library  Membrane Initiated Steroid Signaling Much to be clarified, however what is known now? MISS have a faster biological response. Does not require de novo protein synthesis. Estrogens have been found to have membrane receptors. It is believed that hormone reaches membrane, stimulates receptor and initiates signal transduction pathways (G-protein, PI- 3 kinases, MAP kinase, catalytic processes). Chandar, Nalini and Viselli, Susan. Lippincott's Illustrated Reviews: Cell and Molecular Biology, 2nd Edition Lippincott Williams & Wilkins, a Wolters Kluwer Health Publication, 2019. Available at LWK Health Sciences Library Clinical Application Electrical signal propagation. Action Potentials: AcH at muscle fiber entering Na+. GABA/Glutamate at CNS.  In Summary... Describe the three basic pathways of cell-to-cell signaling. Describe G-protein receptor function, catalytic receptors, and nuclear receptors. Thank you so much for being here! 28  WE MAKE DOCTORS EBM (Evidence Based Medicine) Cabrera-Salaiza