Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-12-21
pubmed:abstractText
Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10567556, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10585470, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10640270, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10666183, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10733577, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-10755621, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-11013214, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-11489946, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-11489947, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-11607816, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-12093790, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-12530980, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-12813469, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-1421168, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9008160, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9008161, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9478921, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9490692, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9697832, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9764820, http://linkedlifedata.com/resource/pubmed/commentcorrection/15611294-9845529
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Dok1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Dok2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Fusion Proteins, bcr-abl, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1, http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
200
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1681-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15611294-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15611294-Animals, pubmed-meshheading:15611294-Bone Marrow, pubmed-meshheading:15611294-Cytokines, pubmed-meshheading:15611294-DNA-Binding Proteins, pubmed-meshheading:15611294-Fusion Proteins, bcr-abl, pubmed-meshheading:15611294-Gene Expression Regulation, Leukemic, pubmed-meshheading:15611294-Granulocyte Precursor Cells, pubmed-meshheading:15611294-Homeostasis, pubmed-meshheading:15611294-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:15611294-Lymphocyte Activation, pubmed-meshheading:15611294-Mice, pubmed-meshheading:15611294-Mice, Knockout, pubmed-meshheading:15611294-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:15611294-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:15611294-Myelopoiesis, pubmed-meshheading:15611294-Phosphoproteins, pubmed-meshheading:15611294-Protein-Serine-Threonine Kinases, pubmed-meshheading:15611294-Proto-Oncogene Proteins, pubmed-meshheading:15611294-Proto-Oncogene Proteins c-akt, pubmed-meshheading:15611294-RNA-Binding Proteins
pubmed:year
2004
pubmed:articleTitle
Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia.
pubmed:affiliation
Dept. of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't