Janus kinase 2 is involved in stromal cell-derived factor-1alpha-induced tyrosine phosphorylation of focal adhesion proteins and migration of hematopoietic progenitor cells

Autor: Xuefeng Zhang, Jerome E. Groopman, Jian Feng Wang, Ewa Matczak, JoAnn Proper
Rok vydání: 2001
Předmět:
Immunology
PTK2
Bone Marrow Cells
Protein tyrosine phosphatase
Biology
Biochemistry
Receptor tyrosine kinase
Focal adhesion
chemistry.chemical_compound
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins
Tumor Cells
Cultured
Humans
Enzyme Inhibitors
Phosphorylation
Phosphotyrosine
Adaptor Proteins
Signal Transducing
Janus kinase 2
Janus kinase 3
Chemotaxis
Nuclear Proteins
Tyrosine phosphorylation
STAT2 Transcription Factor
Cell Biology
Hematology
Janus Kinase 2
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-crk
STAT4 Transcription Factor
Tyrphostins
Hematopoietic Stem Cells
Phosphoproteins
Chemokine CXCL12
Cell biology
DNA-Binding Proteins
Cytoskeletal Proteins
Focal Adhesion Kinase 2
chemistry
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
biology.protein
Cancer research
Trans-Activators
Paxillin
Janus kinase
Cell Adhesion Molecules
Chemokines
CXC
Protein Kinases
Signal Transduction
Zdroj: Blood. 97(11)
ISSN: 0006-4971
Popis: Stromal cell-derived factor-1 (SDF-1), the ligand for the CXCR4 receptor, is a highly efficacious chemoattractant for CD34(+) hematopoietic progenitor cells. However, the SDF-1/CXCR4 signaling pathways that regulate hematopoiesis are still not well defined. This study reports that SDF-1alpha can stimulate the tyrosine phosphorylation of Janus kinase 2 (JAK2) and other members of the JAK/signal transduction and activation of transcription (STAT) family, including JAK1, tyrosine kinase 2, STAT2, and STAT4 in the human progenitor cell line, CTS. SDF-1alpha stimulation of these cells also enhanced the association of JAK2 with phosphatidylinositol 3 (PI3)-kinase. This enhanced association was abolished by pretreatment of cells with AG490, a specific JAK2 inhibitor. Furthermore, pretreatment of CTS cells with AG490 significantly inhibited SDF-1alpha-induced PI3-kinase activity, and inhibition of JAK2 with AG490 ablated the SDF-1alpha-induced tyrosine phosphorylation of multiple focal adhesion proteins (including focal adhesion kinase, related adhesion focal tyrosine kinase, paxillin, CrkII, CrkL, and p130Cas). Chemotaxis assays showed that inhibition of JAK2 diminished SDF-1alpha-induced migration in both CTS cells and CD34(+) human bone marrow progenitor cells. Hence, these results suggest that JAK2 is required for CXCR4 receptor-mediated signaling that regulates cytoskeletal proteins and cell migration through PI3-kinase pathways in hematopoietic progenitor cells. (Blood. 2001;97:3342-3348)
Databáze: OpenAIRE
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