Functional and biochemical association of Hck with the LIF/IL-6 receptor signal transducing subunit gp130 in embryonic stem cells.
The role played by the Src-related tyrosine kinase, Hck, in embryonic stem (ES) cell differentiation was investigated by replacing a conserved C-terminally located tyrosine with phenylalanine by gene targeting. Targeted ES cells display a 7- to 9-fold elevation in constitutive Hck kinase activity and require approximately 15 times less leukaemia inhibitory factor (LIF) than parental ES cells to maintain their stem cell character in vitro. We also demonstrate a rapid and transient increase in Hck tyrosine kinase activity in parental ES cells stimulated by LIF and, finally, show that Hck is physically associated with gp130, an affinity converter and signal transducing component of the LIF receptor. Thus, these results provide biological and biochemical evidence that Hck participates in signal transduction from the LIF receptor.
Ernst
M
M
Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, PO Royal Melbourne Hospital, Victoria, Australia.
Gearing
D P
DP
Dunn
A R
AR
D000818:Animals; D001483:Base Sequence; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051572:Proto-Oncogene Proteins c-hck; D018121:Receptors, Cytokine / Q000378:metabolism*; D018123:Receptors, Interleukin / Q000378:metabolism*; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D011995:Recombination, Genetic; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D011505:Protein-Tyrosine Kinases; D051572:Proto-Oncogene Proteins c-hck