4equ

Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7

Structural highlights

4equ is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

STK10_HUMAN The disease may be caused by mutations affecting the gene represented in this entry.^[1]

Function

STK10_HUMAN Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.^[2] ^[3] ^[4]

Publication Abstract from PubMed

Protein kinases are key components of most mammalian signal transduction networks and are therapeutically relevant drug targets. Efforts to study protein kinase function would benefit from new technologies that are able to profile kinases in complex proteomes. Here, we describe active site-directed probes for profiling kinases in whole cell extracts and live cells. These probes contain general ligands that stabilize a specific inactive conformation of the ATP-binding sites of protein kinases, as well as trifluoromethylphenyl diazirine and alkyne moieties that allow covalent modification and enrichment of kinases, respectively. A diverse group of serine/threonine and tyrosine kinases were identified as specific targets of these probes in whole cell extracts. In addition, a number of kinase targets were selectively labeled in live cells. Our chemical proteomics approach should be valuable for interrogating protein kinase active sites in physiologically relevant environments.

Affinity-Based Probes Based on Type II Kinase Inhibitors.,Ranjitkar P, Perera BG, Swaney DL, Hari SB, Larson ET, Krishnamurty R, Merritt EA, Villen J, Maly DJ J Am Chem Soc. 2012 Nov 6. PMID:23088519^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bignell G, Smith R, Hunter C, Stephens P, Davies H, Greenman C, Teague J, Butler A, Edkins S, Stevens C, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Gillis AJ, Stoop HJ, van Gurp RJ, Oosterhuis JW, Looijenga LH, Futreal PA, Wooster R, Stratton MR. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. PMID:16175573 doi:http://dx.doi.org/10.1002/gcc.20265
↑ Tao L, Wadsworth S, Mercer J, Mueller C, Lynn K, Siekierka J, August A. Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells. Biochem J. 2002 Apr 1;363(Pt 1):175-82. PMID:11903060
↑ Walter SA, Cutler RE Jr, Martinez R, Gishizky M, Hill RJ. Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J Biol Chem. 2003 May 16;278(20):18221-8. Epub 2003 Mar 13. PMID:12639966 doi:http://dx.doi.org/10.1074/jbc.M212556200
↑ Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4707-12. doi:, 10.1073/pnas.0805963106. Epub 2009 Mar 2. PMID:19255442 doi:http://dx.doi.org/10.1073/pnas.0805963106
↑ Ranjitkar P, Perera BG, Swaney DL, Hari SB, Larson ET, Krishnamurty R, Merritt EA, Villen J, Maly DJ. Affinity-Based Probes Based on Type II Kinase Inhibitors. J Am Chem Soc. 2012 Nov 6. PMID:23088519 doi:http://dx.doi.org/10.1021/ja306035v

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Bignell G, Smith R, Hunter C, Stephens P, Davies H, Greenman C, Teague J, Butler A, Edkins S, Stevens C, O'Meara S, Parker A, Avis T, Barthorpe S, Brackenbury L, Buck G, Clements J, Cole J, Dicks E, Edwards K, Forbes S, Gorton M, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jones D, Kosmidou V, Laman R, Lugg R, Menzies A, Perry J, Petty R, Raine K, Shepherd R, Small A, Solomon H, Stephens Y, Tofts C, Varian J, Webb A, West S, Widaa S, Yates A, Gillis AJ, Stoop HJ, van Gurp RJ, Oosterhuis JW, Looijenga LH, Futreal PA, Wooster R, Stratton MR. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Genes Chromosomes Cancer. 2006 Jan;45(1):42-6. PMID:16175573 doi:http://dx.doi.org/10.1002/gcc.20265

[2] Tao L, Wadsworth S, Mercer J, Mueller C, Lynn K, Siekierka J, August A. Opposing roles of serine/threonine kinases MEKK1 and LOK in regulating the CD28 responsive element in T-cells. Biochem J. 2002 Apr 1;363(Pt 1):175-82. PMID:11903060

[3] Walter SA, Cutler RE Jr, Martinez R, Gishizky M, Hill RJ. Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J Biol Chem. 2003 May 16;278(20):18221-8. Epub 2003 Mar 13. PMID:12639966 doi:http://dx.doi.org/10.1074/jbc.M212556200

[4] Belkina NV, Liu Y, Hao JJ, Karasuyama H, Shaw S. LOK is a major ERM kinase in resting lymphocytes and regulates cytoskeletal rearrangement through ERM phosphorylation. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4707-12. doi:, 10.1073/pnas.0805963106. Epub 2009 Mar 2. PMID:19255442 doi:http://dx.doi.org/10.1073/pnas.0805963106

[5] Ranjitkar P, Perera BG, Swaney DL, Hari SB, Larson ET, Krishnamurty R, Merritt EA, Villen J, Maly DJ. Affinity-Based Probes Based on Type II Kinase Inhibitors. J Am Chem Soc. 2012 Nov 6. PMID:23088519 doi:http://dx.doi.org/10.1021/ja306035v

[1]

[2]

[3]

[4]

[5]

4equ

Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

4equ

Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7Human STK-10 (LOK) kinase domain in DFG-out conformation with inhibitor DSA-7

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Search