Cell Signaling (Lecture 2)
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Transcript of Cell Signaling (Lecture 2)
Classification of hormonesLipophillic Hormones with
intracellular receptors e.g steroid, thyroxine, retinoic acid
Hydrophillic with cell-surface receptors e.g peptide hormones (insulin growth factor and glucagon), small charge molecules (epinephrine and histamine)
Lipophillic with cell surface receptor e.g. prostaglandins
Each Cell Is Programmed to Respond to Specific Combinations of Signaling Molecules
Each cell is exposed to many different signals known as combinatorial signaling.
Each cell type displays a set of receptors that enables it to respond to a corresponding set of signaling molecules.
These signaling molecules work in combinations to regulate the behavior of the cell. Many cells require multiple signals ( green arrows) to survive and additional signals ( red arrows) to proliferate; if deprived of all signals, these cells undergo programmed cell death.
General elements of GPCRsMost abundant class of receptorsFound in organisms from yeast to man1. A receptor with 7 membrane-spanning
domains2. A coupled trimeric G protein3. A membrane bound effector protein4. Feedback regulation and desensitization
of the signalling pathway5. A 2nd messenger present in many
GPCRs.
Second messengers are molecules that relay signals from receptors on the cell surface to target molecules inside the cell, in the cytoplasm or nucleus.
These components of GPCRs can be mixed and matched to achieve an astonishing number of different pathways
GPCR pathways usually have short term effects in the cells
Allow the cells to respond rapidly to a variety of signals like environmental stimuli (light) or hormonal stimuli (epinephrine)
General featuresGPCRs have same orientation in
the membrane , 7 transmembrane alpha-helical regions, 4 extra cellular segments, 4 cytosolic segments
The exterior surface of all GPCR consists of hydrophobic amino acids
Amino acids allow the protein to be stably anchored in the hydrophobic core of the plasma membrane
The amino acids are diverseWhich allow different GPCR to bind
very different small moleculesThese small molecules can be
hydrophilic (epinephrine) and hydrophobic (retinol or odorant)
G Protein
Gβ§
•Guanine nucleotide-binding proteins, family of proteins involved in transmitting chemical signals originating from outside a cell into the inside of the cell. •G proteins function as molecular switches. Their activity is regulated by their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). •When they bind GTP, they are 'on', and, when they bind GDP, they are 'off'. •G proteins belong to the larger group of enzymes called GTPases.
Various ligands use G-protein-coupled receptors (GPCRs) to stimulate membrane, cytoplasmic and nuclear targets. GPCRs interact with heterotrimeric G proteins composed of , and subunits that are GDP bound in the resting state. Agonist binding triggers a conformational change in the receptor, which catalyses the dissociation of GDP from the subunit followed by GTP-binding to G and the dissociation of G from G subunits1. The subunits of G proteins are divided into four subfamilies: Gs, Gi, Gq and G12, and a single GPCR can couple to either one or more families of G proteins. Each G protein activates several downstream effectors.
Different G proteins are activated by different GPCRs and inturn regulate different effector proteins.
Effector proteins are in GPCR pathways are either membrane bound ion channels or enzymes that catalyze the formation of the second messengers.
GPCR that regulate ion channelsThe simplest cellular responses to a signal is the
opening or closing of ion channels essential for transmission of nerve impulses
Nerve impulses are essential to the sensory perception of environmental stimuli (light, odor) to transmission of information to and from the brain and to the stimulation of muscle movement
During transmission of nerve impulses, the rapid opening and closing of ion channels causes changes in the membrane potential
Some neurotransmitter receptors are GPCRs whose effector proteins are Na or K channels