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BIO 225

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by: MelLem

BIO 225 BIOL 225

Simmons College
GPA 3.4

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About this Document

cell biology 225. Lecture 14 notes. Insulin Receptors and RTKs. On exam 2, chapter 15.
Cell Biology
Dr. Lopilato
Class Notes
Biology, Cell, Bio, insulin receptors, RTKs.
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Samuel Croteau

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This 3 page Class Notes was uploaded by MelLem on Monday April 4, 2016. The Class Notes belongs to BIOL 225 at Simmons College taught by Dr. Lopilato in Fall 2016. Since its upload, it has received 42 views. For similar materials see Cell Biology in Biology at Simmons College.

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Date Created: 04/04/16
Cell  Bio   Lecture  14       Two  major  types  of  signaling  pathways   • G  Protein  Linked  Receptors      (a)   • Receptor  Protein-­‐Tyrosine  Kinases  (RTKs)      (b)   a b     Receptor  Tyrosine  Kinases  (RTKs)   • RTKS   o Goes  across  the  membrane  only  once   o Ligand  binding  site   o Kinase  activity   • Insulin  Receptor   • Growth  Factor  Receptors   o Growth  factor  receptors  only  go  through  the  membrane  once   o Has  a  ton  of  kinases     Steps  in  the  Activation  of  an  RTK   • 2  different  ways   o ligand  binds  2  receptors  and  brings  them  together  (ligand  mediated   dimerization)   o or  receptors  bring  them  together  after  the  two  different  ligands  have   bound  (Receptor  mediated  dimerization)   • In  both  ways,  the  activated  dimers  go  through  trans-­‐autophosphorylation   and  then  signal  transmission.  At  the  point  of  signal  transmission,  there  is  a   SH2  or  PTB  domain  present  .   • SH2  –  sarc  homology  2   • PTB  –  phosphotyrosine  binding  domain  (binds  to  phosphorylated  tyrosines)     Insulin  RTK   • Function  of  Insulin   o Removed  glucose  from  the  blood   o Stimulate  the  conversion  of  glucose  to  glycogen  (glycogen  is  the     polymer  of  monomers  of  glucose  at  alpha  1,4  glycosidic  bonds)   • Structure  of  RTK  –  tetramer  held  together  by  disulfide  bonds.   o 2  alpha  subunits  –  bind  to  insulin   o 2  beta  subunits    -­‐  kinase  activity   o Insulin  binds  to  its  receptor  and  triggers  a  conformational  change  and   tyrosine  phosphorylation   o As  soon  as  insulin  binds  to  the  alpha  subunit,  the  beta  subunit   phosphorylates.   o Alpha  and  beta  chain  are  linked  together  by  di-­‐sulfide  bonds   o The  insulin  receptor  associates  with  a  small  family  of  adaptor  proteins   called  insulin  receptor  substrates  (IRSs)  which  provide  bonding  sites   for  SH2  domain  containing  signaling  proteins  (PI  3  kinase,  Grb2,  and   Shp2)   o IRS  a  –  protein  that  has  phosphotyrosine  binding  domain  –  insulin   receptor  substrate  (adaptor  proteins)  –  binds  through  PTP,  in  turn  it   gets  phosphorylated.   o Activated  insulin  receptor  phosphorylates  IRS  on  its  tyrosines  as  well   as  phosphorylating  its  own  tyrosines.   o The  tyrosine  phosphorylated  IRS  interacts  with  a  variety  of  proteins   and  activates  a  variety  of  signaling  pathways.     Physiological  Responses  to  Insulin   • Stimulate  glycogen  synthase   • Increase  protein  synthesis   • Use  glucose  in  lipid  synthesis   • **  Transfer  glucose  transporters  to  membrane**   • Activate  Ras  protein  and  stimulate  growth  and  division   • Insulin  binding  stimulates  PI3K  which  produces  PIP3  and  results  in  protein   synthesis,  glucose  uptake,  and  glycogen  synthesis.     Effect  of  insulin  on  glucose  transporters   • When  insulin  levels  rise,  the  transporters  are  brought  to  the  surface  of  the   membrane  by  exocytosis,  at  this  point,  the  glucose  is  able  to  bind  to  the   transporter  and  enter  the  membrane,  following  the  glucose  entering  the  cell,   the  transporters  are  brought  from  the  surface  of  the  membrane  into  the   membrane  through  endocytosis  which  forms  a  membranous  vesicle.       ^  Important  pathways  regarding  glucose  and  insulin.  IR  (insulin  Receptors)  on  the   membrane  surface  start  the  cascade.  


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