_____ protein units function individually Posses no inherent ______ activity Can
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_____ protein units function individually Posses no inherent ______ activity Can activate G-protein complexes one at a time Are ______ receptors (possess ECD, TM, and ICD regions) Activate relay proteins when receptors are activated via _____ binding Initiate ______ pathway(s) when activated relay proteins then activate subsequent proteins and/or second messengers in a series of cascade events (domino effect) Must ____ (2 individual units will couple when each binds ligand) in order to fully activate Possess inherent ______ activity (kinase) Can activate multiple relay proteins simultaneouslyExplanation / Answer
Well, the most important thing to note is the presence of adenylate cyclase resulting in cAMP being formed from ATP and two phosphate groups being liberated. As the receptor accepts a ligand, the alpha unit of the heterotrimeric G-protein attached to the receptor uncouples and attaches to the adenylate cyclase enzyme complex after exchanging GDP (in its inactive, heterotrimeric form) for GTP. This results in a conformational change in structure to adenylate cyclase and "activates" it if you like, so to allow ATP to be hydrolysed. Following this process, the GTP molecule on the alpha unit will be hydrolysed to form GDP, deactivating the alpha unit and reforming the heterotrimeric G protein attached intracellularly to the receptor.
cAMP will then activate a pre-transcription factor (almost always a MAP kinase - which is where the similarity to tyrosine kinase comes in!), resulting in the autophosphorylation of CREBs (cAMP response elements) - THIS itself acts as the transcription factor, as the CREB-phosphate dimer is able to attach to the promoter region to form the transcription-initiation complex and result in transcription by RNA polymerase.
However, the main thing to note about tyrosine kinase is that it activates a phosphorylation CASCADE. As the receptors are bound with the ligand, autophosphorylation of the receptor (via the SRC domain) results in (let's take Growth-receptor binding protein activated by the hormone epidermal growth factor for argument's sake) this protein associating with the receptor and activating SOS (son of sevenless). This causes (similarly to G-protein) a GTP/GDP exchange mechanism whereby Ras (permanently intracellularly on the membrane) to exchange GDP for GTP when activated.
Now this is what activates Raf to result in Raf being converted to MEK via ATP hydrolysis and substrate-level phosphorylation of Raf. MEK is then converted to ERK. This reaction from Raf to ERK is then the phosphorylation cascade. ERK is phosphorylated, so enters the nucleus and exchanges a phosphate group to (so phosphorylates) the transcription factors.
I hope that you have noticed that, although the processes in some ways are very similar (i.e: GTP/GDP exchange mechanism) and subsequent "activation" (conformational structural changes) of a protein (be it adenylate cyclase for the G-protein pathway or Raf for the tyrosine kinase pathway), so that autophosphorylation can subsequently occur.
However, the key differences are that cAMP acts as a secondary messenger to phosphorylate CREB in the G-protein pathway, however, the secondary messenger Raf must undergo a phosphorylation cascade via ATP hydrolysis (this is key - there is no use of ATP in tyrosine kinase), so each protein has a phosphate group added to it in the cascade as ATP is converted to ADP, to form ERK which phosphorylates the transcription factors like CREB.
Have you done JAK/STAT pathway (interferon receptors) yet or phosphatidylinositol 3-kinase (insulin receptor substrate for example) yet? As these are VERY different pathways from G-protein and tyrosine kinase but much simpler to remember and comprehend, where, with the regulation of Janus kinase (JAK), STAT proteins form their own transcription factors but require regulator proteins (like interferon-activated response elements), as this pathway is very prone to mis-transctiption, which is where tyrosine kinase and G-protein pathways step in.
G protein-coupled receptors comprise a large protein family transmembrane receptors.
There are two principal signal transduction pathways involving the G-protein coupled receptors: cAMP signal pathway and Phosphatidylinositol signal pathway. Both activate a G protein ligand binding. G-protein is a trimeric protein. The 3 subunits are called and . The subunit can bind with guanosine diphosphate, GDP. This causes phosphorylation of the GDP to guanosine triphosphate, GTP, and activates the subunit, which then dissociates from the and subunits. The activated subunit can further affect intracellular signaling proteins or target functional proteins directly.
Tyrosine kinase receptors are a family of receptors with a similar structure. They each have a tyrosine kinse domain (which phosphorylates proteins on tyrosine residues), a hormone binding domain, and a carboxyl terminal segment with multiple tyrosines for autophosphorylation.
Ion-channel-linked receptors are also called ligand-gated channels. These membrane-spanning proteins undergo a conformational change when a ligand binds to them so that a "tunnel" is opened through the membrane to allow the passage of a specific molecule. These ligands can be neurotransmitters or peptide hormones, and the molecules that pass through are often ions, such as sodium (Na+) or potassium (K+), which can alter the charge across the membrane. The ion channels, or pores, are opened only for a short time, after which the ligand dissociates from the receptor and the receptor is available once again for a new ligand to bind.
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