Cell Signalling Flashcards
role of kinases in signal amplification
- kinases are enzymes involved in phosphorylation by transferring phosphate groups from ATP to proteins
- protein kinases are involved in phosphorylation cascade whereby each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, bringing about signal amplification
- protein substrates are usually activated when phosphorylated
role of phosphatases in signal amplification
- phosphatases are enzymes that remove phosphate groups from proteins by hydrolysis using a water molecule
- proteins are usually deactivated when dephosphorylated, resulting in signal termination
ligand-receptor interaction in receptor tyrosine kinase
- before ligand binds, receptors exist as individual monomers
- binding of ligand to extracellular binding sites of rtk causes two rtk proteins to come together in a membrane, forming a dimer
- dimerization activates the tyrosine kinase function found in the intracellular tails of rtk
- receptor tail carries out cross-phosphorylation that adds phosphate from ATP to the tyrosine amino acid residues on the tail of the other rtk protein
- activated rtk trigger assembly of relay proteins on receptor tail
- each relay protein undergo structural change, activating them
- activated relay protein triggers a signal transduction pathway, leading to a cellular response
phosphorylation cascade
- protein kinases are enzymes that add phosphate groups from ATP to proteins
- relay molecules are activated when phosphorylated
- each activated relay molecule will initiate a sequential phosphorylation and activation of other downstream relay molecules
- signal amplification occurs when these relay proteins activate other downstream proteins and kinases in a phosphorylation cascade
ligand-receptor interaction in GPLR
- when ligand binds to extracellular site of GPLR, receptor is activated inducing it to change its conformation
- cytoplasmic side of receptor binds to an inactive G protein, causing G protein to exchange its bound GDP for GTP
- G protein activated and dissociates from receptor, binding to an enzyme and activating it
- enzyme triggers a signal transduction pathway leading to cellular response
- when signal molecules is absent, GTP hydrolysed back to GDP by GTPase enzyme
- G protein dissociates from enzyme, returning to its inactive form
second messengers
- small, non-protein, water soluble molecules
- adenylyl cyclase when activated by G protein, can convert many ATP to cAMP molecules
- cAMP is needed to activate protein kinase A by binding to them
- pkA will initiate a sequential activation of downstream kinases, resulting in phosphorylation cascade
- signal amplification occurs and many glycogen phosphorylase are activated for breakdown of glycogen to glucose
specificity of response
- specific type of receptors in specific cell types results in specificity in ligand-receptor interaction
- activation of specific relay molecules within cell trigger specific signal transduction pathways, leading to specific cellular response
glucagon and GPLR signaling
(i) ligand-receptor interaction
- binding of glucagon to extracellular binding site of G-protein linked receptor activates the receptor, causing it to change its conformation
- cytoplasmic side of receptor binds to inactive G protein, causing G protein to exchange its bound GDP for GTP
- G protein is activates and dissociates from receptor, binding and activating adenylyl cyclase, which catalyse conversion of large number of ATP to cAMP molecules
(ii) signal transduction
- cAMP, a second messenger, binds and activates a large number of protein kinase A
- each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, resulting in phosphorylation cascade
- at each phosphorylation step, each activated kinase is able to activate a large number of the next kinase
- at each catalytic step in cascade, number of activated products is always greater than those in the preceeding step
- final protein to be activated is glycogen phosphorylase
(iii) cellular response
- large number of glycogen phosphorylase is activated, catalysing breakdown of glycogen to glucose
(iv) signal termination
- glucagon is released from receptor
- GTPase activity intrinsic to a G protein hydrolyses its bound GTP to GDP
- phosphodiesterase converts cAMP to AMP
insulin and RTK signaling
(i) ligand-receptor interaction
- binding of insulin to extracellular binding site of rtk causes two rtk proteins to form a dimer
- dimerisation activates the tyrosine kinase function found in the intracellular tails of rtk
- tyrosine kinase adds phosphate group from ATP molecule to the tyrosine amino acid residues on the tail of the other RTK protein by autophosphorylation
(ii) signal transduction
- activated rtk triggers the assembly of relay proteins on receptor tails, activating them
- activated relay proteins will further recruit and activate other downstream relay molecules and protein kinase
- each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, resulting in phosphorylation cascade
- at each phosphorylation step, each activated kinase is able to activate a large number of the next kinase
- at each catalytic step, number of activated products is always greater than those in the preceeding step, resulting in signal amplification
(iii) cellular response
- activated relay proteins cause vesicles embedded with glucose transporters to move to cell surface membrane and fuse with it, thus inserting the transporters into the csm, resulting in increase in uptake of glucose into muscle cells
- large number of glycogen synthase activated, catalysing synthesis of glycogen from glucose
(iv) signal termination
- insulin released from receptor, tyrosine residues are dephosphorylated by phosphatases and dimer dissociates back into individual RTK proteins
- protein phosphatases inactivate protein kinases by dephosphorylation
advantages of a cell signaling system
- specificity in ligand-receptor interaction allows signal molecule to elicit responses in specific target cells
- ability of a signal molecule to activate many different target cells simultaneously allow for regulation and control of response
- signal amplification allows for one signal molecule to trigger a large cellular response
- one signal molecule can activate many signal transduction pathways to trigger numerous cellular reactions simultaneously
- binding of signal molecule to receptor at cell surface membrane can result in activation of gene transcription in nucleus
