Tec kinase associates with c-kit and is tyrosine phosphorylated and activated following stem cell factor binding.
Stem cell factor (SCF) plays a crucial role in hematopoiesis through its interaction with the receptor tyrosine kinase c-kit. However, the signaling events that are activated by this interaction and involved in the control of growth or differentiation are not completely understood. We demonstrate here that Tec, a cytoplasmic, src-related kinase, physically associates with c-kit through a region that contains a proline-rich motif, amino terminal of the SH3 domain. Following SCF binding, Tec is tyrosine phosphorylated and its in vitro kinase activity is increased. Tyrosine phosphorylation of Tec is not detected in the response to other cytokines controlling hematopoiesis, including colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-3 (IL-3). Conversely, the cytoplasmic kinase JAK2 is activated by IL-3 but not by SCF stimulation. The activation of distinct cytoplasmic kinases may account for the synergy seen in the actions of SCF and IL-3 on hematopoietic stem cells.
Tang
B
B
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Mano
H
H
Yi
T
T
Ihle
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D006410:Hematopoiesis; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D019000:Phosphotyrosine; D055232:Proline-Rich Protein Domains; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor / Q000378:metabolism*; D019089:Stem Cell Factor; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016298:Hematopoietic Cell Growth Factors; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016184:Receptors, Colony-Stimulating Factor; D019089:Stem Cell Factor; D019000:Phosphotyrosine; D014443:Tyrosine; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases