Sandbox 465: Difference between revisions

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== Function ==

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== Structure ==

STK11 has a molecular mass of approximately 50kDa and is the catalytically active unit of a heterotrimeric complex with STE20-related adaptor (STRAD) and mouse protein 25 (MO25). STRAD, a pseudokinase, induces a conformational change in STK11 to form the catalytically active state which transports STK11 from the nucleus to the cytoplasm. MO25, a scaffold protein, strengthens the interaction between STK11 and STRAD, and as a result enhances the kinase activity of STK11 <ref>

STK11. Genetics Home Reference. National Library of Medicine </ref>. STK11 has a ATP binding site located at Lys78, a basic amino acid, and a <scene name='72/728131/Nucleotide_binding_site/1'>nucleotide binding site</scene> (9 residues) consisting of hydrophobic amino acids (such as Gly, Leu, and Val), hydrophilic amino acids (such as Ser and Tyr), a basic amino acid (Lys), and an acidic amino acid (Glu). STK11 also has an active site at Asp176, which serves as a proton acceptor <ref> Gan RY, Li HB. Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function. International Journal of Molecular Science. 2014 Sep; 15(9):16698-16718. </ref>.

STK11. Genetics Home Reference. National Library of Medicine </ref>. STK11 has a <scene name='72/728131/Atp_binding_site/1'>ATP binding site</scene> located at Lys78, a basic amino acid, and a <scene name='72/728131/Nucleotide_binding_site/1'>nucleotide binding site</scene> (9 residues) consisting of hydrophobic amino acids (such as Gly, Leu, and Val), hydrophilic amino acids (such as Ser and Tyr), a basic amino acid (Lys), and an acidic amino acid (Glu). STK11 also has an <scene name='72/728131/Active_site_1/1'>active site</scene> at Asp176, which serves as a proton acceptor <ref> Gan RY, Li HB. Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function. International Journal of Molecular Science. 2014 Sep; 15(9):16698-16718. </ref>.

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== Disease ==

The function of the STK11 gene is to suppress tumors. A mutation in this protein increases the risk of cancer and carcinomas (cancer arising from the epithelial tissue of internal organs primarily in the gastrointestinal (GI) tract). This is due to improper DNA repair mechanisms and resistance to apoptosis which are both associated to an accumulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) <ref name="PJ"> PMID: 9425897</ref>, particularly p21WAF1 <ref name="loss" />~~. Therefore a mutation in SKT11 leads to CDKN1A malfunction~~. CDKN1A regulates cell development during the G1 and S phase of interphase and activates cyclin-dependent ~~kinase2~~ to regulate apoptosis <ref> PMID: 25329316 </ref>. ~~In addition to cancer~~, a ~~germline~~ mutation of STK11 ~~also increases the chances of Peutz-Jeghers (PJ) syndrome~~, ~~an autosomal genetic dominant mutation caused by a disruption of the kinase domain function. PJ syndrome~~ is characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth <ref name="PJ" />.

The function of the STK11 gene is to suppress tumors. A mutation in this protein increases the risk of cancer and carcinomas (cancer arising from the epithelial tissue of internal organs primarily in the gastrointestinal (GI) tract). Individuals with this germline mutation are diagnosed with Peutz-Jeghers Syndrome (PJS), an autosomal dominant mutation caused by a disruption of the kinase domain. This is due to improper DNA repair mechanisms and resistance to apoptosis which are both associated with an accumulation of cyclin-dependent kinase inhibitor 1A (CDKN1A). <ref name="PJ"> PMID: 9425897</ref>, particularly p21WAF1 <ref name="loss" />. CDKN1A regulates cell development during the G1 and S phase of interphase and activates cyclin-dependent kinase 2 to regulate apoptosis <ref> PMID: 25329316 </ref>. Therefore, a mutation in STK11 leads to CDKN1A malfunction resulting in uncontrolled growth. In addition to cancerous growth, PJS is also characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth <ref name="PJ" />.

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Sandbox 465: Difference between revisions

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-<Structure load='2wtk' size='350' frame='true' align='right' caption=' Serine/Threonine Kinase 11' scene='Insert optional scene name here' />
+<Structure load='2wtk' size='350' frame='true' align='right' caption=' Serine/Threonine Kinase 11 complexed with STRADA and MO25' scene='Insert optional scene name here' />
 == Function ==
@@ Line 15: / Line 15: @@
 == Structure ==
 STK11 has a molecular mass of approximately 50kDa and is the catalytically active unit of a heterotrimeric complex with STE20-related adaptor (STRAD) and mouse protein 25 (MO25). STRAD, a pseudokinase, induces a conformational change in STK11 to form the catalytically active state which transports STK11 from the nucleus to the cytoplasm. MO25, a scaffold protein, strengthens the interaction between STK11 and STRAD, and as a result enhances the kinase activity of STK11 <ref>
-  STK11. Genetics Home Reference. National Library of Medicine </ref>. STK11 has a ATP binding site located at Lys78, a basic amino acid, and a <scene name='72/728131/Nucleotide_binding_site/1'>nucleotide binding site</scene> (9 residues) consisting of hydrophobic amino acids (such as Gly, Leu, and Val), hydrophilic amino acids (such as Ser and Tyr), a basic amino acid (Lys), and an acidic amino acid (Glu). STK11 also has an active site at Asp176, which serves as a proton acceptor <ref> Gan RY, Li HB. Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function. International Journal of Molecular Science. 2014 Sep; 15(9):16698-16718. </ref>.
+  STK11. Genetics Home Reference. National Library of Medicine </ref>. STK11 has a <scene name='72/728131/Atp_binding_site/1'>ATP binding site</scene> located at Lys78, a basic amino acid, and a <scene name='72/728131/Nucleotide_binding_site/1'>nucleotide binding site</scene> (9 residues) consisting of hydrophobic amino acids (such as Gly, Leu, and Val), hydrophilic amino acids (such as Ser and Tyr), a basic amino acid (Lys), and an acidic amino acid (Glu). STK11 also has an <scene name='72/728131/Active_site_1/1'>active site</scene> at Asp176, which serves as a proton acceptor <ref> Gan RY, Li HB. Recent Progress on Liver Kinase B1 (LKB1): Expression, Regulation, Downstream Signaling and Cancer Suppressive Function. International Journal of Molecular Science. 2014 Sep; 15(9):16698-16718. </ref>.
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 == Disease ==
-The function of the STK11 gene is to suppress tumors. A mutation in this protein increases the risk of cancer and carcinomas (cancer arising from the epithelial tissue of internal organs primarily in the gastrointestinal (GI) tract). This is due to improper DNA repair mechanisms and resistance to apoptosis which are both associated to an accumulation of cyclin-dependent kinase inhibitor 1A (CDKN1A) <ref name="PJ"> PMID: 9425897</ref>, particularly p21WAF1 <ref name="loss" />. Therefore a mutation in SKT11 leads to CDKN1A malfunction. CDKN1A regulates cell development during the G1 and S phase of interphase and activates cyclin-dependent kinase2 to regulate apoptosis <ref> PMID: 25329316 </ref>. In addition to cancer, a germline mutation of STK11 also increases the chances of Peutz-Jeghers (PJ) syndrome, an autosomal genetic dominant mutation caused by a disruption of the kinase domain function. PJ syndrome is characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth <ref name="PJ" />.
+The function of the STK11 gene is to suppress tumors. A mutation in this protein increases the risk of cancer and carcinomas (cancer arising from the epithelial tissue of internal organs primarily in the gastrointestinal (GI) tract). Individuals with this germline mutation are diagnosed with Peutz-Jeghers Syndrome (PJS), an autosomal dominant mutation caused by a disruption of the kinase domain. This is due to improper DNA repair mechanisms and resistance to apoptosis which are both associated with an accumulation of cyclin-dependent kinase inhibitor 1A (CDKN1A). <ref name="PJ"> PMID: 9425897</ref>, particularly p21WAF1 <ref name="loss" />. CDKN1A regulates cell development during the G1 and S phase of interphase and activates cyclin-dependent kinase 2 to regulate apoptosis <ref> PMID: 25329316 </ref>. Therefore, a mutation in STK11 leads to CDKN1A malfunction resulting in uncontrolled growth.  In addition to cancerous growth, PJS is also characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth <ref name="PJ" />.
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