Functional dissection of p56lck, a protein tyrosine kinase which mediates interleukin-2-induced activation of the c-fos gene.
Members of the newly identified receptor family for cytokines characteristically lack the intrinsic protein tyrosine kinase domain that is a hallmark of other growth factor receptors. Instead, accumulating evidence suggests that these receptors utilize nonreceptor-type protein tyrosine kinases for downstream signal transduction by cytokines. We have shown previously that the interleukin-2 receptor beta-chain interacts both physically and functionally with a Src family member, p56lck, and that p56lck activation leads to induction of the c-fos gene. However, the mechanism linking p56lck activation with c-fos induction remains unelucidated. In the present study, we systematically examined the extent of c-fos promoter activation by expression of a series of p56lck mutants, using a transient cotransfection assay. The results define a set of the essential amino acid residues that regulate p56lck induction of the c-fos promoter. We also provide evidence that the serum-responsive element and sis-inducible element are both targets through which p56lck controls c-fos gene activation.
Shibuya
H
H
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Kohu
K
K
Yamada
K
K
Barsoumian
E L
EL
Perlmutter
R M
RM
Taniguchi
T
T
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation; D016762:Genes, fos; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D011994:Recombinant Proteins; D017384:Sequence Deletion; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D017931:DNA Primers; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)