Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase

doi:10.1371/journal.pone.0215140

Title: Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase

Abstract

Lyn kinase (Lck/Yes related novel protein tyrosine kinase) belongs to the family of Src-related non-receptor tyrosine kinases. Consistent with physiological roles in cell growth and proliferation, aberrant function of Lyn is associated with various forms of cancer, including leukemia, breast cancer and melanoma. Here, we determine a 1.3 Å resolution crystal structure of the polyproline-binding SH3 regulatory domain of human Lyn kinase, which adopts a five-stranded β-barrel fold. Mapping of cancer-associated point mutations onto this structure reveals that these amino acid substitutions are distributed throughout the SH3 domain and may affect Lyn kinase function distinctly.

Authors:

; Gurevich, Vsevolod V.;

; Boggon, ed., Titus J.

Publication Date:: 2019-04-10

Research Org.:: SLAC National Accelerator Lab., Menlo Park, CA (United States)

Sponsoring Org.:: USDOE Office of Science (SC), Basic Energy Sciences (BES); Office of Science (SC), Biological and Environmental Research (BER)

OSTI Identifier:: 1506167

Alternate Identifier(s):: OSTI ID: 1627880

Grant/Contract Number:: AC02-76SF00515; R35GM122491; GM120569; DA043680

Resource Type:: Published Article

Journal Name:: PLoS ONE

Additional Journal Information:: Journal Name: PLoS ONE Journal Volume: 14 Journal Issue: 4; Journal ID: ISSN 1932-6203

Publisher:: Public Library of Science (PLoS)

Country of Publication:: United States

Language:: English

Subject:: 59 BASIC BIOLOGICAL SCIENCES; Science & Technology - Other Topics

Citation Formats


                    Berndt, Sandra, Gurevich, Vsevolod V., Iverson, T. M., and Boggon, ed., Titus J. Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase.  United States: N. p., 2019. 
        Web.  doi:10.1371/journal.pone.0215140.

Copy to clipboard


                    Berndt, Sandra, Gurevich, Vsevolod V., Iverson, T. M., & Boggon, ed., Titus J. Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase.  United States.  doi:10.1371/journal.pone.0215140.

Copy to clipboard


                    Berndt, Sandra, Gurevich, Vsevolod V., Iverson, T. M., and Boggon, ed., Titus J. Wed .  
        "Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase".  United States.  doi:10.1371/journal.pone.0215140.

Copy to clipboard


                    
@article{osti_1506167,

  title        = {Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase},

  author       = {Berndt, Sandra and Gurevich, Vsevolod V. and Iverson, T. M. and Boggon, ed., Titus J.},

  abstractNote = {Lyn kinase (Lck/Yes related novel protein tyrosine kinase) belongs to the family of Src-related non-receptor tyrosine kinases. Consistent with physiological roles in cell growth and proliferation, aberrant function of Lyn is associated with various forms of cancer, including leukemia, breast cancer and melanoma. Here, we determine a 1.3 Å resolution crystal structure of the polyproline-binding SH3 regulatory domain of human Lyn kinase, which adopts a five-stranded β-barrel fold. Mapping of cancer-associated point mutations onto this structure reveals that these amino acid substitutions are distributed throughout the SH3 domain and may affect Lyn kinase function distinctly.},

  doi          = {10.1371/journal.pone.0215140},

  journal      = {PLoS ONE},

  number       = 4,

  volume       = 14,

  place        = {United States},

  year         = {2019},

  month        = {4}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Publisher's Version of Record
DOI: 10.1371/journal.pone.0215140

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 1 work

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer
journal, June 2015

Reddy, S. M.; Kopetz, S.; Morris, J.
Investigational New Drugs, Vol. 33, Issue 4
DOI: 10.1007/s10637-015-0257-z

Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites
journal, December 2017

Tong, Michael; Pelton, Jeff G.; Gill, Michelle L.
Nature Communications, Vol. 8, Issue 1
DOI: 10.1038/s41467-017-02240-6

Breast cancer patients’ clinical outcome measures are associated with Src kinase family member expression
journal, August 2010

Elsberger, B.; Fullerton, R.; Zino, S.
British Journal of Cancer, Vol. 103, Issue 6
DOI: 10.1038/sj.bjc.6605829

Human germline and pan-cancer variomes and their distinct functional profiles
journal, September 2014

Pan, Yang; Karagiannis, Konstantinos; Zhang, Haichen
Nucleic Acids Research, Vol. 42, Issue 18
DOI: 10.1093/nar/gku772

Recognition and regulation of primary-sequence motifs by signaling modular domains
journal, April 1999

Songyang, Zhou
Progress in Biophysics and Molecular Biology, Vol. 71, Issue 3-4
DOI: 10.1016/S0079-6107(98)00045-5

Comparative Analysis of Human Src-Family Kinase Substrate Specificity in Vitro
journal, November 2010

Takeda, Hiroyuki; Kawamura, Yoshifumi; Miura, Aya
Journal of Proteome Research, Vol. 9, Issue 11
DOI: 10.1021/pr100773t

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases
journal, November 2013

Orchard, Sandra; Ammari, Mais; Aranda, Bruno
Nucleic Acids Research, Vol. 42, Issue D1
DOI: 10.1093/nar/gkt1115

Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients
journal, March 2016

Roseweir, Antonia K.; Qayyum, Tahir; Lim, Zhi
BMC Cancer, Vol. 16, Issue 1
DOI: 10.1186/s12885-016-2254-9

Structural basis for the inhibitor recognition of human Lyn kinase domain
journal, December 2009

Miyano, Nao; Kinoshita, Takayoshi; Nakai, Ryoko
Bioorganic & Medicinal Chemistry Letters, Vol. 19, Issue 23
DOI: 10.1016/j.bmcl.2009.10.038

RT Loop Flexibility Enhances the Specificity of Src Family SH3 Domains for HIV-1 Nef ^† ^, ^‡
journal, October 1998

Arold, Stefan; O'Brien, Ronan; Franken, Peet
Biochemistry, Vol. 37, Issue 42
DOI: 10.1021/bi980989q

Crystal Structures of c-Src Reveal Features of Its Autoinhibitory Mechanism
journal, May 1999

Xu, Wenqing; Doshi, Amish; Lei, Ming
Molecular Cell, Vol. 3, Issue 5
DOI: 10.1016/S1097-2765(00)80356-1

Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity
journal, January 2015

Jin, Lily L.; Wybenga-Groot, Leanne E.; Tong, Jiefei
Molecular & Cellular Proteomics, Vol. 14, Issue 3
DOI: 10.1074/mcp.M114.044404

Crystal Structures of the Lyn Protein Tyrosine Kinase Domain in Its Apo- and Inhibitor-bound State
journal, November 2008

Williams, Neal K.; Lucet, Isabelle S.; Klinken, S. Peter
Journal of Biological Chemistry, Vol. 284, Issue 1
DOI: 10.1074/jbc.M807850200

Crystal Structure Analysis and Solution Studies of Human Lck-SH3; Zinc-induced Homodimerization Competes with the Binding of Proline-rich Motifs
journal, February 2007

Romir, Johannes; Lilie, Hauke; Egerer-Sieber, Claudia
Journal of Molecular Biology, Vol. 365, Issue 5
DOI: 10.1016/j.jmb.2006.10.058

Nintedanib: First Global Approval
journal, November 2014

McCormack, Paul L.
Drugs, Vol. 75, Issue 1
DOI: 10.1007/s40265-014-0335-0

The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck
journal, June 1995

Briggs, Scott D.; Bryant, Sophia S.; Jove, Richard
Journal of Biological Chemistry, Vol. 270, Issue 24
DOI: 10.1074/jbc.270.24.14718

Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors
journal, April 2018

Rupniewska, Ewa; Roy, Rajat; Mauri, Francesco A.
Oncotarget, Vol. 9, Issue 44
DOI: 10.18632/oncotarget.25213

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy
journal, June 2008

Hilberg, F.; Roth, G. J.; Krssak, M.
Cancer Research, Vol. 68, Issue 12
DOI: 10.1158/0008-5472.CAN-07-6307

Dasatinib
journal, September 2006

Kantarjian, Hagop; Jabbour, Elias; Grimley, Joanne
Nature Reviews Drug Discovery, Vol. 5, Issue 9
DOI: 10.1038/nrd2135

The 2.35 å crystal structure of the inactivated form of chicken src: a dynamic molecule with multiple regulatory interactions
journal, December 1997

Williams, John C.; Weijland, Albert; Gonfloni, Stefania
Journal of Molecular Biology, Vol. 274, Issue 5
DOI: 10.1006/jmbi.1997.1426

Activation of the Sire-family tyrosine kinase Hck by SH3 domain displacement
journal, February 1997

Moarefi, Ismail; LaFevre-Bernt, Michelle; Sicheri, Frank
Nature, Vol. 385, Issue 6617
DOI: 10.1038/385650a0

Dynamic Coupling between the SH2 and SH3 Domains of c-Src and Hck Underlies Their Inactivation by C-Terminal Tyrosine Phosphorylation
journal, April 2001

Young, Matthew A.; Gonfloni, Stefania; Superti-Furga, Giulio
Cell, Vol. 105, Issue 1
DOI: 10.1016/S0092-8674(01)00301-4

A Targeted Therapy for Protein and Lipid Kinases in Chronic Lymphocytic Leukemia
journal, November 2012

Robak, P.; Robak, T.
Current Medicinal Chemistry, Vol. 19, Issue 31
DOI: 10.2174/092986712803833371

Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway
journal, April 2015

Toubiana, Julie; Rossi, Anne-Lise; Belaidouni, Nadia
Innate Immunity, Vol. 21, Issue 7
DOI: 10.1177/1753425915586075

The BioGRID interaction database: 2017 update
journal, December 2016

Chatr-aryamontri, Andrew; Oughtred, Rose; Boucher, Lorrie
Nucleic Acids Research, Vol. 45, Issue D1
DOI: 10.1093/nar/gkw1102

Crystallographic structure of the SH3 domain of the human c-Yes tyrosine kinase: Loop flexibility and amyloid aggregation
journal, March 2007

Martín-García, José M.; Luque, Irene; Mateo, Pedro L.
FEBS Letters, Vol. 581, Issue 9
DOI: 10.1016/j.febslet.2007.03.059

Wiki-Pi: A Web-Server of Annotated Human Protein-Protein Interactions to Aid in Discovery of Protein Function
journal, November 2012

Orii, Naoki; Ganapathiraju, Madhavi K.
PLoS ONE, Vol. 7, Issue 11
DOI: 10.1371/journal.pone.0049029

Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity
journal, October 2005

Bauer, Finn; Schweimer, Kristian; Meiselbach, Heike
Protein Science, Vol. 14, Issue 10
DOI: 10.1110/ps.051563605

Dasatinib: An Anti-Tumour Agent via Src Inhibition
journal, April 2011

Gnoni, Antonio; Marech, Ilaria; Silvestris, Nicola
Current Drug Targets, Vol. 12, Issue 4
DOI: 10.2174/138945011794751591

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework
journal, January 2013

Kumar, Gaurav; Breen, Edmond J.; Ranganathan, Shoba
BMC Systems Biology, Vol. 7, Issue 1
DOI: 10.1186/1752-0509-7-12

Molecular basis for regulation of Src by the docking protein p130Cas
journal, January 2005

Nasertorabi, Fariborz; Tars, Kaspars; Becherer, Kathleen
Journal of Molecular Recognition, Vol. 19, Issue 1
DOI: 10.1002/jmr.755

A proline to glycine mutation in the Lck SH3-domain affects conformational sampling and increases ligand binding affinity
journal, March 2007

Bauer, Finn; Sticht, Heinrich
FEBS Letters, Vol. 581, Issue 8
DOI: 10.1016/j.febslet.2007.03.012

A critical role for Lyn in acute myeloid leukemia
journal, February 2008

Dos Santos, Cédric; Demur, Cécile; Bardet, Valérie
Blood, Vol. 111, Issue 4
DOI: 10.1182/blood-2007-04-082099

Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors
journal, January 2015

Vohidov, Farrukh; Knudsen, Sarah E.; Leonard, Paul G.
Chemical Science, Vol. 6, Issue 8
DOI: 10.1039/C5SC01602A

Features and development of Coot
journal, March 2010

Emsley, P.; Lohkamp, B.; Scott, W. G.
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4
DOI: 10.1107/S0907444910007493

BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery
journal, October 2017

Dingerdissen, Hayley M.; Torcivia-Rodriguez, John; Hu, Yu
Nucleic Acids Research, Vol. 46, Issue D1
DOI: 10.1093/nar/gkx907

Solution structure and peptide binding of the SH3 domain from human Fyn
journal, June 1996

Morton, Craig J.; Pugh, David JR; Brown, Emma LJ
Structure, Vol. 4, Issue 6
DOI: 10.1016/S0969-2126(96)00076-7

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
DOI: 10.1107/S0907444909052925

Functions of the Lyn tyrosine kinase in health and disease
journal, January 2012

Ingley, Evan
Cell Communication and Signaling, Vol. 10, Issue 1
DOI: 10.1186/1478-811X-10-21

Phaser.MRage : automated molecular replacement
journal, October 2013

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.
Acta Crystallographica Section D Biological Crystallography, Vol. 69, Issue 11
DOI: 10.1107/S0907444913022750

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors
journal, May 2016

Zafra Ruano, Ana; Cilia, Elisa; Couceiro, José R.
PLOS Computational Biology, Vol. 12, Issue 5
DOI: 10.1371/journal.pcbi.1004938

The SH3 domain of Src can downregulate its kinase activity in the absence of the SH2 domain-pY527 interaction
journal, August 2002

Brábek, Jan; Mojžita, Dominik; Novotný, Marian
Biochemical and Biophysical Research Communications, Vol. 296, Issue 3
DOI: 10.1016/S0006-291X(02)00884-7

The Protein Kinase Complement of the Human Genome
journal, December 2002

Manning, G.
Science, Vol. 298, Issue 5600
DOI: 10.1126/science.1075762

dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs
journal, January 2016

Liu, Xiaoming; Wu, Chunlei; Li, Chang
Human Mutation, Vol. 37, Issue 3
DOI: 10.1002/humu.22932

SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src
journal, January 1998

Thomas, Jeffrey W.; Ellis, Byron; Boerner, Renee J.
Journal of Biological Chemistry, Vol. 273, Issue 1
DOI: 10.1074/jbc.273.1.577

Cooperative activation of Src family kinases by SH3 and SH2 ligands
journal, November 2007

Yadav, Shalini S.; Miller, W. Todd
Cancer Letters, Vol. 257, Issue 1
DOI: 10.1016/j.canlet.2007.07.012

Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide
journal, October 2002

Donaldson, L. W.; Gish, G.; Pawson, T.
Proceedings of the National Academy of Sciences, Vol. 99, Issue 22
DOI: 10.1073/pnas.212518799

Structures of Src-family tyrosine kinases
journal, December 1997

Sicheri, Frank; Kuriyan, John
Current Opinion in Structural Biology, Vol. 7, Issue 6
DOI: 10.1016/S0959-440X(97)80146-7

Crystal Structure of the Src Family Kinase Hck SH3-SH2 Linker Regulatory Region Supports an SH3-dominant Activation Mechanism
journal, September 2010

Alvarado, John J.; Betts, Laurie; Moroco, Jamie A.
Journal of Biological Chemistry, Vol. 285, Issue 46
DOI: 10.1074/jbc.M110.145102

Three-dimensional structure of the tyrosine kinase c-Src
journal, February 1997

Xu, Wenqing; Harrison, Stephen C.; Eck, Michael J.
Nature, Vol. 385, Issue 6617
DOI: 10.1038/385595a0

Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors
journal, May 2004

Lannutti, Brian J.; Drachman, Jonathan G.
Blood, Vol. 103, Issue 10
DOI: 10.1182/blood-2003-10-3566

Phaser crystallographic software
journal, July 2007

McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D.
Journal of Applied Crystallography, Vol. 40, Issue 4
DOI: 10.1107/S0021889807021206

Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway
journal, February 2013

Croucher, D. R.; Hochgrafe, F.; Zhang, L.
Cancer Research, Vol. 73, Issue 6
DOI: 10.1158/0008-5472.CAN-12-1472

Similar Records in DOE PAGES and OSTI.GOV collections:

Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

Journal Article Kükenshöner, Tim ; Schmit, Nadine Eliane ; Bouda, Emilie ; ... - Journal of Molecular Biology

The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroupmore »« less
DOI: 10.1016/j.jmb.2017.03.023
Chromosomal location of the Syk and ZAP-70 tyrosine kinase genes in mice and humans

Journal Article Ku, G ; Malissen, B ; Mattei, M G - Immunogenetics

Several protein tyrosine kinases (PTKs), which may be grouped into two structurally different families, have been implicated in antigen receptor proximal signaling. Blk, Fyn, Lck, Lyn, and Yes belong to the Src-family kinases, whereas the spleen tyrosine kinase (Syk) and the CD3-{zeta}-associated PTK (ZAP-70) define a new one, the Syk family. These kinases differ from the Src-family kinases in that they are non-myristylated cytoplasmic polypeptides composed of two N-terminal Src homology-2 (SH2) domains and a C-terminal catalytic domain. ZAP-70 appears to be expressed exclusively in T cells and NK cells, whereas Syk is preferentially expressed in B cells, T cells,more » and myeloid cells. 15 refs., 2 figs.« less
DOI: 10.1007/BF00189976
Role of lymphocyte-specific protein tyrosine kinase (LCK) in the expansion of glioma-initiating cells by fractionated radiation

Journal Article Kim, Rae-Kwon ; Yoon, Chang-Hwan ; Hyun, Kyung-Hwan ; ... - Biochemical and Biophysical Research Communications

Research highlights: {yields} Activation of Lymphocyte-specific protein tyrosine kinase (LCK) is involved in the fractionated radiation-induced expansion of glioma stem-like cells. {yields} Inhibition of LCK prevents acquisition of fractionated radiation-induced resistance to chemotherapeutic treatment. {yields} LCK activity is critical for the maintenance of self-renewal in glioma stem-like cells. -- Abstract: Brain cancers frequently recur or progress as focal masses after treatment with ionizing radiation. Radiation used to target gliomas may expand the cancer stem cell population and enhance the aggressiveness of tumors; however, the mechanisms underlying the expansion of cancer stem cell population after radiation have remained unclear. In thismore »« less
DOI: 10.1016/J.BBRC.2010.10.072
Lyn tyrosine kinase promotes silencing of ATM-dependent checkpoint signaling during recovery from DNA double-strand breaks

Journal Article Fukumoto, Yasunori ; Kuki, Kazumasa ; Morii, Mariko ; ... - Biochemical and Biophysical Research Communications

Highlights: • Inhibition of Src family kinases decreased γ-H2AX signal. • Inhibition of Src family increased ATM-dependent phosphorylation of Chk2 and Kap1. • shRNA-mediated knockdown of Lyn increased phosphorylation of Kap1 by ATM. • Ectopic expression of Src family kinase suppressed ATM-mediated Kap1 phosphorylation. • Src is involved in upstream signaling for inactivation of ATM signaling. - Abstract: DNA damage activates the DNA damage checkpoint and the DNA repair machinery. After initial activation of DNA damage responses, cells recover to their original states through completion of DNA repair and termination of checkpoint signaling. Currently, little is known about the processmore »« less
DOI: 10.1016/J.BBRC.2014.08.113
Crystal structure of the kinase domain of human protein tyrosine kinase 6 (PTK6) at 2.33 Å resolution

Journal Article Thakur, Manish Kumar ; Department of Structural Biology, Jubilant Biosys Ltd, Bangalore, 560022 ; Kumar, Amit ; ... - Biochemical and Biophysical Research Communications

Human Protein tyrosine kinase 6 (PTK6) (EC:2.7.10.2), also known as the breast tumor kinase (BRK), is an intracellular non-receptor Src-related tyrosine kinase expressed in a majority of human breast tumors and breast cancer cell lines, but its expression is low or completely absent in normal mammary glands. In the recent past, several studies have suggested that PTK6 is a potential therapeutic target in cancer. To understand its structural and functional properties, the PTK6 kinase domain (PTK6-KD) gene was cloned, overexpressed in a baculo-insect cell system, purified and crystallized at room temperature. X-ray diffraction data to 2.33 Å resolution was collected onmore »« less
DOI: 10.1016/J.BBRC.2016.07.121

Similar Records

Title: Crystal structure of the SH3 domain of human Lyn non-receptor tyrosine kinase

Abstract

Citation Formats

Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer journal, June 2015

Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites journal, December 2017

Breast cancer patients’ clinical outcome measures are associated with Src kinase family member expression journal, August 2010

Human germline and pan-cancer variomes and their distinct functional profiles journal, September 2014

Recognition and regulation of primary-sequence motifs by signaling modular domains journal, April 1999

Comparative Analysis of Human Src-Family Kinase Substrate Specificity in Vitro journal, November 2010

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases journal, November 2013

Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients journal, March 2016

Structural basis for the inhibitor recognition of human Lyn kinase domain journal, December 2009

RT Loop Flexibility Enhances the Specificity of Src Family SH3 Domains for HIV-1 Nef † , ‡ journal, October 1998

Crystal Structures of c-Src Reveal Features of Its Autoinhibitory Mechanism journal, May 1999

Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity journal, January 2015

Crystal Structures of the Lyn Protein Tyrosine Kinase Domain in Its Apo- and Inhibitor-bound State journal, November 2008

Crystal Structure Analysis and Solution Studies of Human Lck-SH3; Zinc-induced Homodimerization Competes with the Binding of Proline-rich Motifs journal, February 2007

Nintedanib: First Global Approval journal, November 2014

The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck journal, June 1995

Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors journal, April 2018

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy journal, June 2008

Dasatinib journal, September 2006

The 2.35 å crystal structure of the inactivated form of chicken src: a dynamic molecule with multiple regulatory interactions journal, December 1997

Activation of the Sire-family tyrosine kinase Hck by SH3 domain displacement journal, February 1997

Dynamic Coupling between the SH2 and SH3 Domains of c-Src and Hck Underlies Their Inactivation by C-Terminal Tyrosine Phosphorylation journal, April 2001

A Targeted Therapy for Protein and Lipid Kinases in Chronic Lymphocytic Leukemia journal, November 2012

Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway journal, April 2015

The BioGRID interaction database: 2017 update journal, December 2016

Crystallographic structure of the SH3 domain of the human c-Yes tyrosine kinase: Loop flexibility and amyloid aggregation journal, March 2007

Wiki-Pi: A Web-Server of Annotated Human Protein-Protein Interactions to Aid in Discovery of Protein Function journal, November 2012

Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity journal, October 2005

Dasatinib: An Anti-Tumour Agent via Src Inhibition journal, April 2011

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework journal, January 2013

Molecular basis for regulation of Src by the docking protein p130Cas journal, January 2005

A proline to glycine mutation in the Lck SH3-domain affects conformational sampling and increases ligand binding affinity journal, March 2007

A critical role for Lyn in acute myeloid leukemia journal, February 2008

Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors journal, January 2015

Features and development of Coot journal, March 2010

BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery journal, October 2017

Solution structure and peptide binding of the SH3 domain from human Fyn journal, June 1996

PHENIX: a comprehensive Python-based system for macromolecular structure solution journal, January 2010

Functions of the Lyn tyrosine kinase in health and disease journal, January 2012

Phaser.MRage : automated molecular replacement journal, October 2013

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors journal, May 2016

The SH3 domain of Src can downregulate its kinase activity in the absence of the SH2 domain-pY527 interaction journal, August 2002

The Protein Kinase Complement of the Human Genome journal, December 2002

dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs journal, January 2016

SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src journal, January 1998

Cooperative activation of Src family kinases by SH3 and SH2 ligands journal, November 2007

Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide journal, October 2002

Structures of Src-family tyrosine kinases journal, December 1997

Crystal Structure of the Src Family Kinase Hck SH3-SH2 Linker Regulatory Region Supports an SH3-dominant Activation Mechanism journal, September 2010

Three-dimensional structure of the tyrosine kinase c-Src journal, February 1997

Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors journal, May 2004

Phaser crystallographic software journal, July 2007

Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway journal, February 2013

Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer
journal, June 2015

Survey of solution dynamics in Src kinase reveals allosteric cross talk between the ligand binding and regulatory sites
journal, December 2017

Breast cancer patients’ clinical outcome measures are associated with Src kinase family member expression
journal, August 2010

Human germline and pan-cancer variomes and their distinct functional profiles
journal, September 2014

Recognition and regulation of primary-sequence motifs by signaling modular domains
journal, April 1999

Comparative Analysis of Human Src-Family Kinase Substrate Specificity in Vitro
journal, November 2010

The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases
journal, November 2013

Nuclear expression of Lyn, a Src family kinase member, is associated with poor prognosis in renal cancer patients
journal, March 2016

Structural basis for the inhibitor recognition of human Lyn kinase domain
journal, December 2009

RT Loop Flexibility Enhances the Specificity of Src Family SH3 Domains for HIV-1 Nef ^† ^, ^‡
journal, October 1998

Crystal Structures of c-Src Reveal Features of Its Autoinhibitory Mechanism
journal, May 1999

Tyrosine Phosphorylation of the Lyn Src Homology 2 (SH2) Domain Modulates Its Binding Affinity and Specificity
journal, January 2015

Crystal Structures of the Lyn Protein Tyrosine Kinase Domain in Its Apo- and Inhibitor-bound State
journal, November 2008

Crystal Structure Analysis and Solution Studies of Human Lck-SH3; Zinc-induced Homodimerization Competes with the Binding of Proline-rich Motifs
journal, February 2007

Nintedanib: First Global Approval
journal, November 2014

The Ras GTPase-activating Protein (GAP) Is an SH3 Domain-binding Protein and Substrate for the Src-related Tyrosine Kinase, Hck
journal, June 1995

Targeting autophagy sensitises lung cancer cells to Src family kinase inhibitors
journal, April 2018

BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy
journal, June 2008

Dasatinib
journal, September 2006

The 2.35 å crystal structure of the inactivated form of chicken src: a dynamic molecule with multiple regulatory interactions
journal, December 1997

Activation of the Sire-family tyrosine kinase Hck by SH3 domain displacement
journal, February 1997

Dynamic Coupling between the SH2 and SH3 Domains of c-Src and Hck Underlies Their Inactivation by C-Terminal Tyrosine Phosphorylation
journal, April 2001

A Targeted Therapy for Protein and Lipid Kinases in Chronic Lymphocytic Leukemia
journal, November 2012

Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway
journal, April 2015

The BioGRID interaction database: 2017 update
journal, December 2016

Crystallographic structure of the SH3 domain of the human c-Yes tyrosine kinase: Loop flexibility and amyloid aggregation
journal, March 2007

Wiki-Pi: A Web-Server of Annotated Human Protein-Protein Interactions to Aid in Discovery of Protein Function
journal, November 2012

Structural characterization of Lyn-SH3 domain in complex with a herpesviral protein reveals an extended recognition motif that enhances binding affinity
journal, October 2005

Dasatinib: An Anti-Tumour Agent via Src Inhibition
journal, April 2011

Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework
journal, January 2013

Molecular basis for regulation of Src by the docking protein p130Cas
journal, January 2005

A proline to glycine mutation in the Lck SH3-domain affects conformational sampling and increases ligand binding affinity
journal, March 2007

A critical role for Lyn in acute myeloid leukemia
journal, February 2008

Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors
journal, January 2015

Features and development of Coot
journal, March 2010

BioMuta and BioXpress: mutation and expression knowledgebases for cancer biomarker discovery
journal, October 2017

Solution structure and peptide binding of the SH3 domain from human Fyn
journal, June 1996

PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

Functions of the Lyn tyrosine kinase in health and disease
journal, January 2012

Phaser.MRage : automated molecular replacement
journal, October 2013

From Binding-Induced Dynamic Effects in SH3 Structures to Evolutionary Conserved Sectors
journal, May 2016

The SH3 domain of Src can downregulate its kinase activity in the absence of the SH2 domain-pY527 interaction
journal, August 2002

The Protein Kinase Complement of the Human Genome
journal, December 2002

dbNSFP v3.0: A One-Stop Database of Functional Predictions and Annotations for Human Nonsynonymous and Splice-Site SNVs
journal, January 2016

SH2- and SH3-mediated Interactions between Focal Adhesion Kinase and Src
journal, January 1998

Cooperative activation of Src family kinases by SH3 and SH2 ligands
journal, November 2007

Structure of a regulatory complex involving the Abl SH3 domain, the Crk SH2 domain, and a Crk-derived phosphopeptide
journal, October 2002

Structures of Src-family tyrosine kinases
journal, December 1997

Crystal Structure of the Src Family Kinase Hck SH3-SH2 Linker Regulatory Region Supports an SH3-dominant Activation Mechanism
journal, September 2010

Three-dimensional structure of the tyrosine kinase c-Src
journal, February 1997

Lyn tyrosine kinase regulates thrombopoietin-induced proliferation of hematopoietic cell lines and primary megakaryocytic progenitors
journal, May 2004

Phaser crystallographic software
journal, July 2007

Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway
journal, February 2013