User:Joseph Lipsick/SRC: Difference between revisions

<scene name='User:Joseph_Lipsick/SRC/Sh1/3'>SH1</scene> comprises the catalytic protein kinase.  Within SH1 is <scene name='User:Joseph_Lipsick/SRC/Tyr416/1'>TYR416</scene> which must be phosphorylated for full kinase activity.  In contrast, when <scene name='User:Joseph_Lipsick/SRC/Phospho-tyr527/1'>TYR527</scene> which lies carboxy-terminal to the SH1 domain is phosphorylated, the kinase is inactive.  Phosphorylation of TYR527 greatly diminshed phosphrylation of TYR416.  Removal of TYR527 by truncation (as in V-SRC) or by substitution with PHE (by site-directed mutagenesis) causes constitutive activation of the kinase.  SH2 domains were shown to bind to peptide containing phosphotyrosine.  In particular, the <scene name='User:Joseph_Lipsick/SRC/Sh2/1'>SH2</scene> domain of C-SRC binds to phospho-TYR527.  Although this binding is reversible, the bound state predominates.  This bound state prevents the kinase from phosphorylating substrates.  Dephosphorylation of TYR527 results in an <scene name='User:Joseph_Lipsick/SRC/Activated_c-src/1'>opening</scene> of the protein structure by release of the SH2 domain.  The loop which contains TYR416 and occludes the active site of the SH1 kinase domain is phosphorylated first.  phospho-TYR416 alters the conformation of this loop, resulting in a dramatic increase in protein kinase activity.  SH3 domains were shown to bind to peptides with multiple adjacent proline residues.  The SH3 domain of C-SRC binds to the SH2 domain of C-SRC, helping to stabilize the active form of the kinase.