Cell Communications and Signal Transduction

F. Ferdinal

Biochemistry and Molecular Biology Tarumanagara Univ. Sch of Med

Introduction to Cell Signaling

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ENDOCRINE HORMONES CAN BE CLASSIFIED IN SEVERAL WAYS chemical composition solubility properties location of receptors nature of the signal used to mediate hormonal action Classification of Hormones by Mechanism of Action I. Hormones that bind to intracellular receptors Androgens Mineralocorticoids Calcitriol Progestins Estrogens Retinoic acid Glucocorticoids Thyroid hormones (T3 and T4 ) II. Hormones that bind to cell surface receptors

A. The second messenger is cAMP

2-Adrenergic catecholamines 1-Adrenergic catecholamines Adrenocorticotropic hormone (ACTH) Antidiuretic hormone Calcitonin Chorionic gonadotropin, human (CG) Corticotropin-releasing hormone Follicle-stimulating hormone (FSH) Glucagon Lipotropin (LPH) Luteinizing hormone (LH) Melanocyte-stimulating hormone (MSH) Parathyroid hormone (PTH) Somatostatin Thyroid-stimulating hormone (TSH)

B. The second messenger is cGMP

Atrial Natriuretic Peptide (ANP) B-type Natriuretic Peptide (BNP)
Acetylcholine (muscarinic) 1-Adrenergic catecholamines Angiotensin II ADH (vasopressin) Cholecystokinin (CCK) Gastrin
Adiponectin Chorionic Somatomammotropin Epidermal Growth Factor (EGF) Erythropoietin (EPO) Fibroblast Growth Factor (FGF) Growth Hormone (GH) Platelet-Derived Growth Factor (PDGF)

Nitric oxide (NO) Carbonmonoxide (CO)

GnRH Oxytocin PDGF Substance P TRH

C. The second messenger is Ca or PI (or both)

D. Second messenger is a kinase or phosphatase cascade

IGF I and II Leptin Nerve Growth Factor (N Insulin Prolactin

Stimulation Adenylate Cyclasel (Hs)

ACTH ADH -Adrenergics Calcitonin Somatostatin CRH FSH Glucagon hCG LH LPH MSH, PTH, TSH TSH

Inhibition (Hi)
Acetylcholine 2 -Adrenergics Angiotensin II Somatostatin

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Membrane Receptor Classes

Figure 6-5: Four classes of membrane receptors

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Some of important Receptors

GPCR

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RTK

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Family of Nuclear Receptor Proteins

Divided into 6 domains (A F) : A/B (AF-1): modulator, DBD, LBD, AF-2

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Response of a target cell to a hormone

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OverOverview of Signal Transduction Pathways

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1. Adenylate Cyclase Signaling Pathway

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2. Phosphoinositide (PI-3K) Signaling System

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3.MAPK Signaling Pathways

MAPK Signaling Pathways

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4.THE JAK/STAT SIGNALING PATHWAY

(LIGAND: GH, Prolactin, EPO and CYTOKINES)
( STAT / Signal Transducers and Activators of Transcription )

5.Insulin Signaling Pathways

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6.Leptin Signaling Pathway

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7.NFB Signaling Pathway

8.Notch/Delta Signaling Pathway

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Notch/Delta Signaling Pathway

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9.Hh/Hedgehog Signaling Pathway

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8.Hh/Hedgehog Signaling Pathway

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10.Wnt Signaling Pathway

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Overview Wnt Signaling Pathway

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Overview PI3K/AKT Survival Signaling Pathway

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11.PI3K/AKT (Survival) Signaling Pathway

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12.ROS Signaling Pathway

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13.Hypoxia Signaling Pathway

14.Hypertrophy Signaling Pathway

Interaction of cells to matrix requires specific receptors

laminin

Cells adhere to ECM via specialized cell surface receptors. The most important of these are INTEGRINS. Integrins are heterodimeric transmembrane proteins which Depending on their subunit composition bind to distinct ECM Ligands.
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Functions of the extracellular matrix

- Provides structural/mechanical support for cells and tissues
- Provides signals for survival, morphogenesis/differentiation, migration, proliferation

Properties of the extracellular matrix

- Binds and modulates activity of growth factors - It is dynamic in nature - undergoes constant remodeling

Components of the Extracellular Matrix

Structural Glycoproteins FibriIlar Proteins Glycosaminoglycans and Proteoglycans Catalytic Matrix Metalloproteinases ADAMS ADAMTS Inhibitors MMP INHIBITORS - TIMPS

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Cell-Cell Interactions are Mediated by Four Major Families of Proteins

1) Cadherins
E-Cadherins -- Epithelial N-Cadherins -- Neuronal VE-Cadherins -- Vascular Endothelium P-Cadherins -- Placenta

2) Some members of the Ig (Immunoglobulin Super Family) 3) Integrins 4) Selectin

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15. APOPTOSIS (Programmed Cell Death/PCD)

Many TK inhibitors identified: Key for success - SPECIFICITY

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Membrane Receptor Classes

Figure 6-5: Four classes of membrane receptors

Signal Pathways
Signal molecule (ligand) Receptor Intracellular signal Target protein Response

Figure 6-3: Signal pathways

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