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4eih

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Revision as of 00:05, 5 August 2016

Crystal structure of Arg SH2 domain

Structural highlights

4eih is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	ABL2, ABLL, ARG (HUMAN)
Activity:	Non-specific protein-tyrosine kinase, with EC number 2.7.10.2
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[ABL2_HUMAN] Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 acts also as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

The closely related Abl family kinases, Arg and Abl, play important non-redundant roles in the regulation of cell morphogenesis and motility. Despite similar N-terminal sequences, Arg and Abl interact with different substrates and binding partners with varying affinities. This selectivity may be due to slight differences in amino acid sequence leading to differential interactions with target proteins. We report that the Arg Src homology (SH) 2 domain binds two specific phosphotyrosines on cortactin, a known Abl/Arg substrate, with over 10-fold higher affinity than the Abl SH2 domain. We show that this significant affinity difference is due to the substitution of arginine 161 and serine 187 in Abl to leucine 207 and threonine 233 in Arg, respectively. We constructed Abl SH2 domains with R161L and S187T mutations alone and in combination and find that these substitutions are sufficient to convert the low affinity Abl SH2 domain to a higher affinity "Arg-like" SH2 domain in binding to a phospho-cortactin peptide. We crystallized the Arg SH2 domain for structural comparison to existing crystal structures of the Abl SH2 domain. We show that these two residues are important determinants of Arg and Abl SH2 domain binding specificity. Finally, we expressed Arg containing an "Abl-like" low affinity mutant Arg SH2 domain (L207R/T233S) and find that this mutant, although properly localized to the cell periphery, does not support wild type levels of cell edge protrusion. Together, these observations indicate that these two amino acid positions confer different binding affinities and cellular functions on the distinct Abl family kinases.

Two amino Acid residues confer different binding affinities of abelson family kinase SRC homology 2 domains for phosphorylated cortactin.,Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ J Biol Chem. 2014 Jul 11;289(28):19704-13. doi: 10.1074/jbc.M114.556480. Epub, 2014 Jun 2. PMID:24891505^[6]

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

References

↑ Hu H, Bliss JM, Wang Y, Colicelli J. RIN1 is an ABL tyrosine kinase activator and a regulator of epithelial-cell adhesion and migration. Curr Biol. 2005 May 10;15(9):815-23. PMID:15886098 doi:10.1016/j.cub.2005.03.049
↑ Cao C, Li Y, Leng Y, Li P, Ma Q, Kufe D. Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress. Oncogene. 2005 Apr 7;24(15):2433-40. PMID:15735735 doi:10.1038/sj.onc.1208454
↑ Liu X, Huang W, Li C, Li P, Yuan J, Li X, Qiu XB, Ma Q, Cao C. Interaction between c-Abl and Arg tyrosine kinases and proteasome subunit PSMA7 regulates proteasome degradation. Mol Cell. 2006 May 5;22(3):317-27. PMID:16678104 doi:10.1016/j.molcel.2006.04.007
↑ Boyle SN, Michaud GA, Schweitzer B, Predki PF, Koleske AJ. A critical role for cortactin phosphorylation by Abl-family kinases in PDGF-induced dorsal-wave formation. Curr Biol. 2007 Mar 6;17(5):445-51. Epub 2007 Feb 15. PMID:17306540 doi:10.1016/j.cub.2007.01.057
↑ Yogalingam G, Pendergast AM. Abl kinases regulate autophagy by promoting the trafficking and function of lysosomal components. J Biol Chem. 2008 Dec 19;283(51):35941-53. doi: 10.1074/jbc.M804543200. Epub 2008, Oct 21. PMID:18945674 doi:10.1074/jbc.M804543200
↑ Gifford SM, Liu W, Mader CC, Halo TL, Machida K, Boggon TJ, Koleske AJ. Two amino Acid residues confer different binding affinities of abelson family kinase SRC homology 2 domains for phosphorylated cortactin. J Biol Chem. 2014 Jul 11;289(28):19704-13. doi: 10.1074/jbc.M114.556480. Epub, 2014 Jun 2. PMID:24891505 doi:http://dx.doi.org/10.1074/jbc.M114.556480

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4eih"

@@ Line 1: / Line 1: @@
 ==Crystal structure of Arg SH2 domain==
 <StructureSection load='4eih' size='340' side='right' caption='[[4eih]], [[Resolution|resolution]] 1.20&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ABL2, ABLL, ARG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4eih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eih OCA], [http://pdbe.org/4eih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4eih RCSB], [http://www.ebi.ac.uk/pdbsum/4eih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4eih ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4eih" style="background-color:#fffaf0;"></div>
 ==See Also==

4eih

From Proteopedia

Revision as of 00:05, 5 August 2016

Crystal structure of Arg SH2 domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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