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"accession": "cd05067",
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"source_database": "cdd",
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"name": {
"name": "Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk",
"short": "PTKc_Lck_Blk"
},
"description": [
{
"text": "<p>PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. [[cite:PUB00118868], [cite:PUB00118869], [cite:PUB00086113], [cite:PUB00041723], [cite:PUB00086111], [cite:PUB00044007], [cite:PUB00118870], [cite:PUB00118871], [cite:PUB00118872], [cite:PUB00052515], [cite:PUB00118873], [cite:PUB00086342], [cite:PUB00118874], [cite:PUB00116892]]</p>",
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"PMID": 16257509,
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"volume": "18",
"issue": "8",
"year": 2006,
"title": "Lck couples Shc to TCR signaling.",
"URL": null,
"raw_pages": "1182-9",
"medline_journal": "Cell Signal",
"ISO_journal": "Cell. Signal.",
"authors": [
"Fukushima A",
"Hatanaka Y",
"Chang JW",
"Takamatsu M",
"Singh N",
"Iwashima M."
],
"DOI_URL": "https://doi.org/10.1016/j.cellsig.2005.09.008"
},
"PUB00118872": {
"PMID": 17082661,
"ISBN": null,
"volume": "177",
"issue": "10",
"year": 2006,
"title": "Atorvastatin restores Lck expression and lipid raft-associated signaling in T cells from patients with systemic lupus erythematosus.",
"URL": null,
"raw_pages": "7416-22",
"medline_journal": "J Immunol",
"ISO_journal": "J Immunol",
"authors": [
"Jury EC",
"Isenberg DA",
"Mauri C",
"Ehrenstein MR."
],
"DOI_URL": null
},
"PUB00086113": {
"PMID": 15489916,
"ISBN": null,
"volume": "23",
"issue": "48",
"year": 2004,
"title": "Function of the Src-family kinases, Lck and Fyn, in T-cell development and activation.",
"URL": null,
"raw_pages": "7990-8000",
"medline_journal": "Oncogene",
"ISO_journal": "Oncogene",
"authors": [
"Palacios EH",
"Weiss A."
],
"DOI_URL": "https://doi.org/10.1038/sj.onc.1208074"
},
"PUB00118871": {
"PMID": 15899916,
"ISBN": null,
"volume": "106",
"issue": "5",
"year": 2005,
"title": "Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn.",
"URL": null,
"raw_pages": "1703-10",
"medline_journal": "Blood",
"ISO_journal": "Blood",
"authors": [
"Lowenberg M",
"Tuynman J",
"Bilderbeek J",
"Gaber T",
"Buttgereit F",
"van Deventer S",
"Peppelenbosch M",
"Hommes D."
],
"DOI_URL": null
},
"PUB00116892": {
"PMID": 16581827,
"ISBN": null,
"volume": "291",
"issue": "2",
"year": 2006,
"title": "Src protein tyrosine kinase family and acute inflammatory responses.",
"URL": null,
"raw_pages": "L129-41",
"medline_journal": "Am J Physiol Lung Cell Mol Physiol",
"ISO_journal": "Am J Physiol Lung Cell Mol Physiol",
"authors": [
"Okutani D",
"Lodyga M",
"Han B",
"Liu M."
],
"DOI_URL": null
},
"PUB00118870": {
"PMID": 15687496,
"ISBN": null,
"volume": "280",
"issue": "14",
"year": 2005,
"title": "Expression of CD45 lacking the catalytic protein tyrosine phosphatase domain modulates Lck phosphorylation and T cell activation.",
"URL": null,
"raw_pages": "14318-24",
"medline_journal": "J Biol Chem",
"ISO_journal": "J Biol Chem",
"authors": [
"Wang Y",
"Johnson P."
],
"DOI_URL": null
},
"PUB00041723": {
"PMID": 17118402,
"ISBN": null,
"volume": "365",
"issue": "5",
"year": 2007,
"title": "Crystal structure analysis and solution studies of human Lck-SH3; zinc-induced homodimerization competes with the binding of proline-rich motifs.",
"URL": null,
"raw_pages": "1417-28",
"medline_journal": "J Mol Biol",
"ISO_journal": "J. Mol. Biol.",
"authors": [
"Romir J",
"Lilie H",
"Egerer-Sieber C",
"Bauer F",
"Sticht H",
"Muller YA."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.jmb.2006.10.058"
},
"PUB00118874": {
"PMID": 10879287,
"ISBN": null,
"volume": "75",
"issue": null,
"year": 2000,
"title": "Tyrosine kinase activation in the decision between growth, differentiation, and death responses initiated from the B cell antigen receptor.",
"URL": null,
"raw_pages": "283-316",
"medline_journal": "Adv Immunol",
"ISO_journal": "Adv Immunol",
"authors": [
"Hsueh RC",
"Scheuermann RH."
],
"DOI_URL": null
},
"PUB00118869": {
"PMID": 16186791,
"ISBN": null,
"volume": "25",
"issue": "12",
"year": 2006,
"title": "A novel link between Lck, Bak expression and chemosensitivity.",
"URL": null,
"raw_pages": "1693-5",
"medline_journal": "Oncogene",
"ISO_journal": "Oncogene",
"authors": [
"Heyninck K",
"Beyaert R."
],
"DOI_URL": null
},
"PUB00044007": {
"PMID": 17276681,
"ISBN": null,
"volume": "17",
"issue": "8",
"year": 2007,
"title": "Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties.",
"URL": null,
"raw_pages": "2299-304",
"medline_journal": "Bioorg Med Chem Lett",
"ISO_journal": "Bioorg. Med. Chem. Lett.",
"authors": [
"Martin MW",
"Newcomb J",
"Nunes JJ",
"Bemis JE",
"McGowan DC",
"White RD",
"Buchanan JL",
"DiMauro EF",
"Boucher C",
"Faust T",
"Hsieh F",
"Huang X",
"Lee JH",
"Schneider S",
"Turci SM",
"Zhu X."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.bmcl.2007.01.048"
},
"PUB00086342": {
"PMID": 10648608,
"ISBN": null,
"volume": "20",
"issue": "4",
"year": 2000,
"title": "The B-cell-specific Src-family kinase Blk is dispensable for B-cell development and activation.",
"URL": null,
"raw_pages": "1227-33",
"medline_journal": "Mol Cell Biol",
"ISO_journal": "Mol. Cell. Biol.",
"authors": [
"Texido G",
"Su IH",
"Mecklenbrauker I",
"Saijo K",
"Malek SN",
"Desiderio S",
"Rajewsky K",
"Tarakhovsky A."
],
"DOI_URL": "https://doi.org/10.1128/MCB.20.4.1227-1233.2000"
},
"PUB00118868": {
"PMID": 16611580,
"ISBN": null,
"volume": "23",
"issue": "1",
"year": 2006,
"title": "Lipid rafts in T cell receptor signalling .",
"URL": null,
"raw_pages": "49-57",
"medline_journal": "Mol Membr Biol",
"ISO_journal": "Mol Membr Biol",
"authors": [
"Kabouridis PS."
],
"DOI_URL": null
},
"PUB00118873": {
"PMID": 14970218,
"ISBN": null,
"volume": "279",
"issue": "19",
"year": 2004,
"title": "Isoforms of the Ets transcription factor NERF/ELF-2 physically interact with AML1 and mediate opposing effects on AML1-mediated transcription of the B cell-specific blk gene.",
"URL": null,
"raw_pages": "19512-22",
"medline_journal": "J Biol Chem",
"ISO_journal": "J Biol Chem",
"authors": [
"Cho JY",
"Akbarali Y",
"Zerbini LF",
"Gu X",
"Boltax J",
"Wang Y",
"Oettgen P",
"Zhang DE",
"Libermann TA."
],
"DOI_URL": null
},
"PUB00052515": {
"PMID": 14662906,
"ISBN": null,
"volume": "198",
"issue": "12",
"year": 2003,
"title": "Mimicry of pre-B cell receptor signaling by activation of the tyrosine kinase Blk.",
"URL": null,
"raw_pages": "1863-73",
"medline_journal": "J Exp Med",
"ISO_journal": "J. Exp. Med.",
"authors": [
"Tretter T",
"Ross AE",
"Dordai DI",
"Desiderio S."
],
"DOI_URL": "http://dx.doi.org/10.1084/jem.20030729"
}
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"accession": "cl21453",
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"accession": "4c3f",
"name": "Structure of Lck in complex with a compound discovered by Virtual Fragment Linking"
}
}
}
