User:Joseph Lipsick/SRC: Difference between revisions
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<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 <scene name='User:Joseph_Lipsick/SRC/Sh3/1'>SH3</scene> domain of C-SRC binds to the SH2 domain of C-SRC, thereby helping to stabilize the conformation of the entire protein. | <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 <scene name='User:Joseph_Lipsick/SRC/Sh3/1'>SH3</scene> domain of C-SRC binds to the SH2 domain of C-SRC, thereby helping to stabilize the conformation of the entire protein. | ||
<scene name='User:Joseph_Lipsick/SRC/ | <scene name='User:Joseph_Lipsick/SRC/Inactive_c-src/1'>INACTIVE C-SRC</scene> | ||
<scene name='User:Joseph_Lipsick/SRC/Activated_c-src/1'>ACTIVATED C-SRC</scene> | <scene name='User:Joseph_Lipsick/SRC/Activated_c-src/1'>ACTIVATED C-SRC</scene> | ||
Revision as of 05:26, 16 March 2009
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The c-src proto-oncogene encodes a protein tyrosine kinase. The v-src oncogene of the Rous sarcoma virus encodes a mutated, activated form of this enzyme. In particular, the virally encoded V-SRC protein lacks the carboxyl-terminus of the normal C-SRC protein. Phosphopeptide mapping and site-directed mutagenesis revealed the importance of two tyrosine (TYR) residues that are critical for the activity and regulation of C-SRC, TYR416 and TYR527. Insertional mutagenesis and comparisons with other proteins revealed the presence of three highly conserved SRC Homology domains, SH1, SH2, and SH3. SH1 comprises the catalytic protein kinase. Within SH1 is TYR416 which must be phosphorylated for full kinase activity. In contrast, when TYR527 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 SH2 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 opening 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, thereby helping to stabilize the conformation of the entire protein.
