PTEN: Difference between revisions

Mutations of PTEN occur within of the these different areas of the protein.  The P-loop itself contains three mutations all of which decrease the protein's activity. This results in excessive cells growth and tumors.  The amino acid mutated in the loop are <scene name='Nathan_Line_sandbox/P_mutations/1'>Lys125, Lys128, and His123</scene>, which decrease the protein's activity from 50-60%.  The "TI" loop also contain mutations.  These include mutations of <scene name='Nathan_Line_sandbox/Ti_mutations/1'>Thr167 and Gln171.</scene>  Though the Gln171 mutation is not directly inside the "TI" loop, its close proximity does affect the loop's function.  These mutations decrease the activity by 60% and 75%.  Even though this loop is not a part of the catalysis, its decreased interactions with the lipid hinders the catalytic reactions of the P-loop.  In addition to the active loops in the phosphatase domain, the C2 domain also contains mutations that affect the protein's ability to interact with the membrane.  This mutation is located at the <scene name='Nathan_Line_sandbox/C2_mutations/1'>Leu345</scene> which is mutated to a Gln.  There are several mutations located along some of the general portions of the protein.  The most influencial of of these is the mutation of <scene name='Nathan_Line_sandbox/Other_mutations1/2'>Asp92</scene> to Ala.  This mutation alone causes a 700-fold reduction in the protein's catalytic activity.  The last set of general mutations are involved in the interdomain hydrogen bonding the takes place between the two domains.  Of the several amino acids that are incorporated into the hydrogen bonding, <scene name='Nathan_Line_sandbox/Other_mutations2/1'>Ser170 and Arg173</scene> are among the eight most frequently mutated residues of PTEN.  The severe decrease in phosphatase activity due to these mutations confirms the extreme importance of this interface for PTEN function.