test 3 Flashcards
alpha G protein (active for signaling) + GTP>can activate downstream; alpha G protein+GDP (inactive); GAP to go from active alpha G to inactive and GTP/GEF to do the reverse; beta and gamma subunits dissociate from activated G-protein alpha subunit
GPCRs and trimeric G proteins
these processes are for quick changes in physiology of organism, part of this is the second messengers; activity of the alpha subunit if terminated by hydrolysis of the bound GTP, which is stimulated by RGS proteins, the inactive GDP-bound alpha subunit then reassociates with beta/gamma complex>in the inactive state, the alpha subunit is bound to GDP in a complex with beta and gamma>hormone binding stimulates the release of GDP and its exchange for GTP; the activated GTP-bound alpha subunit and beta/gamma complex then dissociate from the receptor and interact with their targets
activation of trimeric G proteins
activation of GPCRs can lead to the production of second messengers-properties=small molecules or ions (can rapidly diffuse), lots of molecules can be produced quickly (unlike synthesizing a new protein
GCPRs and second messengers
can lead to enzyme activation, gene transcription and activation of other signaling pathways; short-lived due to break down by cAMP phosphodiesterase
production and degradation of cAMP
cAMP is made when adenylyl cyclase is activated modifying regulatory subunit of protein kinase A which activates catalytic subunit allowing it to diffuse into nuclease
PKA can activate cystolic and nuclear proteins
PLC breaks PIP2 down into membrane-associated DAG and cystolic IP3; both of these are signaling molecules and can change function of things
production of IP3 and DAG
cell metabolism, cell division, cell movement, cell differentiation, cell survival, cell electrical activity, transcription
signaling pathways can modulate
activation of downstream components: extracellular signal molecule>receptor protein>plasma membrane>intracellular signaling proteins>effector proteins (metabolic enzyme>altered metabolism, transcription regulatory protein>altered gene expression, cytoskeletal protein>altered cell shape or movement); signal amplification
basic components of a signal transduction pathway
direct cell-cell signaling: both signaling molecules are transmembrane proteins (receptor binding a ligand on the cell); paracrine signaling: nearby, one cell producing some sort of ligand that is acting on cells close by; autocrine signaling: a cell will secrete its own ligand and their receptor would change
short range signaling
hormones must diffuse via the blood stream (effects can take years to manifest), uses different hormones to communicate specifically with their target cell, hormones are very dilute in the blood stream and must show great specificity for their receptor, hormones-must be made away from their site of action, be transported, work at physiological concentrations (made by glands)
long range signaling-endocrine signaling
can be on the cell surface or intracellular
different receptors
nuclear receptors: act as transcription factors to directly alter gene expression, ligand-gated ion channels: respond to neurotransmitters and enable ion flows across membrane, G-protein coupled receptors: respond to signals by activating intracellular trimeric G-proteins that in turn elicit cellular responses, enzyme coupled receptors: respond to a variety of signals and are either enzymes themselves or directly associated with an enzyme
four major classes of signaling receptors
direct protein transport through the nuclear pore complex; inactive in the absence of hormone-Glucocorticoids diffuse across the plasma membrane and bind to the glucocorticoid receptor, absence of ligand, the receptor is bound to Hsp90, Glucocorticoid binding causes conformational changes that displace the receptor from Hsp90 and expose nuclear localization signals, allowing nuclear import as receptor dimers, the activated receptors then bind recognition sites in DNA and associate with coactivators with histone acetyltransferase (HAT) activity to stimulate transcription of their target genes; active receptor
nuclear receptors
an ion channel that opens in response to the binding of signaling molecules, no permanently open and highly selective
ligand-gated ion channels
a receptor characterized by seven membrane-spanning α helices, ligand binding causes a conformational change that activates a G protein; heterotrimeric G proteins, binding of hormone promotes the interaction of the receptor with a heterotrimeric G protein composed of α, β, and γ subunits and with GDP bound to its α subunit, activated receptor acts as GEF and GDP released and GTP bound to alpha subunit which can activate targets, many G-proteins in cells, molecular switches and drug targets
G-coupled protein receptor
phospholipids structural and bioactive, sterols (neutral polycyclic membrane lipid), types of sterols present varies by kingdom, sphingolipids-generally bioactive, bioactive molecules temporally regulated and maintained at low levels
lipid components of plasma membrane
structural proteins that interact with extracellular matrices (e.g. collagen fiber or cell walls), receptors and signaling complexes, transport proteins (e.g. ion channels, pumps)
protein components of plasma membrane
proteins do not remain static, PM is always moving and renewing itself
protein mobility in the membrane
refrigerated centrifugation opened the door to enzymatic studies of subcellular compartments, follow with enzymatic assay or western blot, treatment of obtained fractions can help determine membrane associations, molecular bio and confocal microscopy opened the door to many more types of studies
differential centrifugation
high salt dissociates peripheral proteins, reducing agent disrupts disulfide linkages, strong detergent removes integral membrane proteins
membrane associations
membrane fragments that remain intact with mild detergent treatment, enriched in sterols and signaling machinery/molecules
lipid rafts/detergent resistant microdomains
