Sandbox Reserved 598: Difference between revisions

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[[Image:MyJak2.jpg|thumb|250px|left|Not, "just another kinase". Picture from Protein Data Bank.]]

Janus Kinase 2 is a non-receptor janus kinase, a protein which is part of the tyrosine kinases. These group of kinases are the primary intracellular mediators of cytokine signaling and are involved in the control of cellular growth. As a non-receptor kinase, Jak 2 has a cytoplasmic enzyme which catalyzes the transfer of a phosphate group through phosphorylation to the tyrosine residue in the protein. Such an enzyme plays a crucial role in regulating various cellular functions by switching on or off additional enzymes within the cell. <ref> Hanks, SK., Quinn, AM., Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241 (4861): 42–52. doi:10.1126/science.3291115. PMID 3291115. </ref> Such phosphorylation is a reversible process, and used in many different pathways as a method to control cellular activity. However kinases like Jak2, have enzymes which add phosphate groups to hydroxyl side chains as can be seen in the diagram. <ref> Hudel, H. [Internet]. Irvine [CA]. Center for Biomembrane Systems at UC Irvine; c2013. [Updated 2013 Jan 3; cited 2013 March 23]. Available from: http://bass.bio.uci.edu </ref> ~~[[Image:Phosphorylation.png]]~~

Janus Kinase 2 is a non-receptor janus kinase, a protein which is part of the tyrosine kinases. These group of kinases are the primary intracellular mediators of cytokine signaling and are involved in the control of cellular growth. As a non-receptor kinase, Jak 2 has a cytoplasmic enzyme which catalyzes the transfer of a phosphate group through phosphorylation to the tyrosine residue in the protein. Such an enzyme plays a crucial role in regulating various cellular functions by switching on or off additional enzymes within the cell. <ref> Hanks, SK., Quinn, AM., Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241 (4861): 42–52. doi:10.1126/science.3291115. PMID 3291115. </ref> Such phosphorylation is a reversible process, and used in many different pathways as a method to control cellular activity. However kinases like Jak2, have enzymes which add phosphate groups to hydroxyl side chains as can be seen in the diagram. <ref> Hudel, H. [Internet]. Irvine [CA]. Center for Biomembrane Systems at UC Irvine; c2013. [Updated 2013 Jan 3; cited 2013 March 23]. Available from: http://bass.bio.uci.edu </ref>

Jak2 was given its name "Janus" after the two-faced Roman God "Janus" who was known as the custodian of the universe and the God of new beginnings. <ref> Janus incarnate [Internet]. Kirwan Studios; c2011. [Updated 2011 Feb 3; cited 2013 March 23' Retrieved from http://rense.com/general92/janus.htm http://rense.com/general92/janus.htm </ref> The abbreviation 'Jak' is commonly referred to as 'just another kinase' as, when it was first discovered, the kinase's role was not yet fully understood. <ref> Weinberg, I. (April 2010). Janus Kinase (Jak2)”. Vascular Medicind; Angiolgist http://www.angiologist.com/general-medicine/janus-kinase-2-jak2/ </ref>

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There are currently many therapies for differing forms of leukemia, some of which include cytoreductive medications such as hydroxyurea or agrylin, to suppress the bone marrow’s ability to make blood cells, cell destructive medications like cytoxin which act as oral chemotheraputic agents, interferon treatments to stimulate the patient's immune response to fight and kill overproduction or white and red blood cells. Finally traditional chemotherapy is commonly used, as well, for both leukemias as well as progressive polycythemia vera. <ref> Acute Myeloid Leukemia [Internet]. Bethesda [MD]. The National Cancer Institute; c2013. [Updated 2013 March 06; cited 2013 March 23]. Available from: http://m.cancer.gov/topics/treatment/bycancer/adultAML/Patient </ref> <ref> Chronic Lymphocytic Leukemia [Internet]. Rochester [Mn]. The Mayo Clinic; c2011. [Updated 2011 Apr 7; cited 2013 March 23]. Available from: http://www.mayoclinic.com/health/chronic-lymphocytic-leukemia/DS00565 </ref> <ref> Polycythemia Vera [Internet]. Rochester [Mn]. The Mayo Clinic; c2011. [Updated 2011 Apr 7; cited 2013 March 23]. Available from: http://www.mayoclinic.com/health/polycythemia-vera/DS00919 </ref> <ref> Polycythemia Treatment and Management [Internet]. Medscape; 2012. [Updated 2012 Jan 10; cited 2013 March 23]. Available from: http://emedicine.medscape.com/article/205114-treatment </ref> While there are a few Jak2 inhibitors already in use which use competitive inhibition for ATP binding pockets, they are not extremely effective due to non-specificity. Due to this issue with specificity, the current therapies for Jak2 mutations are being more focused on allosteric inhibition designs. This research is believed to be hopeful due to the successes it has had with other, different, kinase inhibition. Possible sites which scientists are targeting for such inhibition include, the type II Inhibitor pocket, substrate binding sites, kinase pseudo kinase domain interface, SH2JK2 Linker Region, and the FERM Domain. Currently many of these are in both pre and post clinical trials. <ref> Gnanasambandan, K., & Sayeski, P. (2011). A structure-function perspective of jak2 mutations and implications for alternate drug design strategies: the road not taken. Department of Physiology and Functional Genomics, University of Florida College of Medicine, 18(30), 59-73. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21864276 http://www.ncbi.nlm.nih.gov/pubmed/21864276 </ref> A brief discussion on diseases associated with Jak2, as well as the function of the protein can be found on an already established Proteopedia page found at [[2b7a]].

~~{{STRUCTURE_2b7a| PDB=2b7a | SCENE= }}~~

==References==

Sandbox Reserved 598: Difference between revisions

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@@ Line 8: / Line 8: @@
 [[Image:MyJak2.jpg|thumb|250px|left|Not, "just another kinase". Picture from Protein Data Bank.]]
-Janus Kinase 2 is a non-receptor janus kinase, a protein which is part of the tyrosine kinases. These group of kinases are the primary intracellular mediators of cytokine signaling and are involved in the control of cellular growth. As a non-receptor kinase, Jak 2 has a cytoplasmic enzyme which catalyzes the transfer of a phosphate group through phosphorylation to the tyrosine residue in the protein.  Such an enzyme plays a crucial role in regulating various cellular functions by switching on or off additional enzymes within the cell. <ref> Hanks, SK., Quinn, AM., Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241 (4861): 42–52. doi:10.1126/science.3291115. PMID 3291115. </ref> Such phosphorylation is a reversible process, and used in many different pathways as a method to control cellular activity. However kinases like Jak2, have enzymes which add phosphate groups to hydroxyl side chains as can be seen in the diagram. <ref> Hudel, H. [Internet]. Irvine [CA]. Center for Biomembrane Systems at UC Irvine; c2013. [Updated 2013 Jan 3; cited 2013 March 23]. Available from: http://bass.bio.uci.edu </ref> [[Image:Phosphorylation.png]]
+Janus Kinase 2 is a non-receptor janus kinase, a protein which is part of the tyrosine kinases. These group of kinases are the primary intracellular mediators of cytokine signaling and are involved in the control of cellular growth. As a non-receptor kinase, Jak 2 has a cytoplasmic enzyme which catalyzes the transfer of a phosphate group through phosphorylation to the tyrosine residue in the protein.  Such an enzyme plays a crucial role in regulating various cellular functions by switching on or off additional enzymes within the cell. <ref> Hanks, SK., Quinn, AM., Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241 (4861): 42–52. doi:10.1126/science.3291115. PMID 3291115. </ref> Such phosphorylation is a reversible process, and used in many different pathways as a method to control cellular activity. However kinases like Jak2, have enzymes which add phosphate groups to hydroxyl side chains as can be seen in the diagram. <ref> Hudel, H. [Internet]. Irvine [CA]. Center for Biomembrane Systems at UC Irvine; c2013. [Updated 2013 Jan 3; cited 2013 March 23]. Available from: http://bass.bio.uci.edu </ref>
 Jak2 was given its name "Janus" after the two-faced Roman God "Janus" who was known as the custodian of the universe and the God of new beginnings. <ref> Janus incarnate [Internet]. Kirwan Studios; c2011. [Updated 2011 Feb 3; cited 2013 March 23' Retrieved from http://rense.com/general92/janus.htm http://rense.com/general92/janus.htm </ref> The abbreviation 'Jak' is commonly referred to as 'just another kinase' as, when it was first discovered, the kinase's role was not yet fully understood. <ref> Weinberg, I. (April 2010). Janus Kinase (Jak2)”. Vascular Medicind; Angiolgist http://www.angiologist.com/general-medicine/janus-kinase-2-jak2/ </ref>
@@ Line 40: / Line 40: @@
 There are currently many therapies for differing forms of leukemia, some of which include cytoreductive medications such as hydroxyurea or agrylin, to suppress the bone marrow’s ability to make blood cells, cell destructive medications like cytoxin which act as oral chemotheraputic agents, interferon treatments to stimulate the patient's immune response to fight and kill overproduction or white and red blood cells. Finally traditional chemotherapy is commonly used, as well, for both leukemias as well as progressive polycythemia vera. <ref> Acute Myeloid Leukemia [Internet]. Bethesda [MD]. The National Cancer Institute; c2013. [Updated 2013 March 06; cited 2013 March 23]. Available from: http://m.cancer.gov/topics/treatment/bycancer/adultAML/Patient </ref> <ref> Chronic Lymphocytic Leukemia [Internet]. Rochester [Mn]. The Mayo Clinic; c2011. [Updated 2011 Apr 7; cited 2013 March 23]. Available from: http://www.mayoclinic.com/health/chronic-lymphocytic-leukemia/DS00565 </ref> <ref> Polycythemia Vera [Internet]. Rochester [Mn]. The Mayo Clinic; c2011. [Updated 2011 Apr 7; cited 2013 March 23]. Available from: http://www.mayoclinic.com/health/polycythemia-vera/DS00919 </ref> <ref> Polycythemia Treatment and Management [Internet]. Medscape; 2012. [Updated 2012 Jan 10; cited 2013 March 23]. Available from: http://emedicine.medscape.com/article/205114-treatment </ref> While there are a few Jak2 inhibitors already in use which use competitive inhibition for ATP binding pockets, they are not extremely effective due to non-specificity. Due to this issue with specificity, the current therapies for Jak2 mutations are being more focused on allosteric inhibition designs. This research is believed to be hopeful due to the successes it has had with other, different, kinase inhibition. Possible sites which scientists are targeting for such inhibition include, the type II Inhibitor pocket, substrate binding sites, kinase pseudo kinase domain interface, SH2JK2 Linker Region, and the FERM Domain. Currently many of these are in both pre and post clinical trials. <ref> Gnanasambandan, K., & Sayeski, P. (2011). A structure-function perspective of jak2 mutations and implications for alternate drug design strategies: the road not taken. Department of Physiology and Functional Genomics, University of Florida College of Medicine, 18(30), 59-73. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21864276 http://www.ncbi.nlm.nih.gov/pubmed/21864276 </ref> A brief discussion on diseases associated with Jak2, as well as the function of the protein can be found on an already established Proteopedia page found at [[2b7a]].
-{{STRUCTURE_2b7a|  PDB=2b7a  |  SCENE=  }}
 ==References==
 <references />