Toipc 1 Principle of Cell Signaling

• Describe the principle of cell signalling.

  Upon binding of the extracellular signal molecule and cell receptor, this triggers the generation of intracellular signalling proteins. These proteins lead to the formation of effector proteins which carry out specific cell response.
• What are the 4 types of cell signalling?

  1. Contact-dependent
  2. Paracrine
  3. Synaptic
  4. Endocrine
• What causes the response to be cell type dependent?

  The signal molecule carries very little information, however, each type of cells are programmed to respond differently. Thus, the intracellular signalling proteins, effector proteins and gene activated are responsible for the unique response.
• Cell receptors can be classified into which two types?

  Cell-surface receptors: Cell-surface receptors are embedded in the plasma membrane of the cell. Upon binding with hydrophilic signalling molecules, it will induce biological response.

  
  

  Intracellular receptors: Intracellular receptors are located within the cell. To induce a biological response, the hydrophobic signalling molecule first needs to penetrate the phospholipid bilayer and bind to the intracellular receptor within the cell.
• What are the three types of cell surface receptors?

  Ion channels, G protein-coupled receptors, and enzyme-linked receptors.
• Ion-channel recceptor: Transmission of nerve impulse

  
  

  Enzyme receptor: Receptor tyrosin kinase (fibroblast growth factor), serine/threonine-specific protein kinase (bone morphogenetic protein), and guanylate cyclase (atrial natriuretic factor receptor)

  
  

  G-protein recpetor: Behavioral and mood regulation & Automatic nervoues system transmission
• Intracellular signalling molecules can be “switched on” by which two process.

  1. Phosphorylation
  2. GTP-binding
• What are the three types of signalling complexes?

  
  

  
  

  • Assembly of signalling complexes on an activated receptor
  • Assembly of signalling complexes on phosphoinositide docking site
  • Preformed signalling complex on a scaffold protein
• What are the signalling molecules of G-protein-coupled protein?

  • Cyclic AMP (cAMP)
  • Phosphatidylinositol 4, 5 biphosphate (PIP2)
  • Ca2+/Calmodulin
• What are the signalling molecules of enzyme-coupled receptor?

  -Phosphorylated tyrosine

  -Ras

  -MAP kinase
• Nuclear receptor is a signalling molecules of intracellular receptor.
• What type of signalling molecules is for cell-surface receptors?

  Hydrophillic signalling molecules.
• What type of signalling molecules is for intracellular receptors?

  Hydrophobic signalling molecules.
• G-protein coupled receptors are seven-transmembrane protein with a heterotrimeric G-protein consists of three different subunits. (α, β, γ)
• What is the role of Calmodulin in physiological processes?

  The calmodulin is responsible for the activation of phosphorylase kinase which leads to glucose being cleaved from glycogen. It exerts its effect on calcitonin that responsible for lipid metabolism as well as lowering blood Ca2+ level. Moreover, the calmodulin also activates the G protein cascade that leads to cAMP generation.
• Serine/threonine protein kinase is a class of enzyme in the family of transferases that transfer phosphates to the oxygen atom of a serine or threonine side chain in protein. This process is known as phosphorylation.
• What is the fate of GDP on the G-protein, upon binding of signalling molecule to the Gprotein-coupled receptor??

  The binding of signalling molecules on G-protein-coupled receptor induces conformational change in the G-protein which leads to dissociation of GDP and replace by GTP. The GTP in turns activate the G-protein to initiate further cell signalling processes.
• What is role of cAMP in G-protein-coupled receptor?

  The cAMP is known as cyclic adenosine 3’,5’monophosphate that act as a vital second messenger involve in numerous physiological processes (e.g. metabolism, muscle contraction, cell proliferation, cell survival, cell apoptosis and gene expression).

  
  

  Upon activation by G-alpha subunit, the adenylate cyclase (AC) synthesize cAMP from ATP whereas the phosphpdiesterase (PDE) degrade the cAMP to AMP. It acts directly on protein kinase A (PKA), the exchange protein activated by cAMP (Epac) and cyclic nucleotide-gated ion channels (CHGCs)
• What are the characteristics of inositol 1, 4, 5-triphosphate (IP3) and diacylglycerol (DAG)?

  
  

  Briefly indicate their location inside a cell. IP3: Hydrophilic; diffuse to cytosol and bind to endoplasmic reticulum DAG: Hydrophobic; remain at the phospholipid bilayer and interact with protein kinase C (PKC)
• Which enzyme is involved in the hydrolysis of phosphatidylinositol 4, 5 biphosphate (PIP2)?

  What are the products of hydrolysis. The activated phospholipase C is responsible for the hydrolysis of PIPS which cleaves it into inositol 1, 4, 5-triphosphate (IP3) and diacylglycerol (DAG)