We are investigating the consequences of mitogen mediated signals to T cells by isolating and characterizing genes that constitute the immediate early transcriptional response to these events. We have isolated over 60 novel cDNA clones that represent mRNA species induced by PHA and PMA in human peripheral blood T cells. We initially have selected clones for complete sequencing analyses whose expression was shown to be restricted in tissue specificity or constitutively high in adult T cell leukemia (ATL) cells. Primary sequence analysis on seven clones has been completed. Three clones restricted in expression to hematopoietic cells encode two related but nonidentical lymphokines (464 and 744) and a cell surface protein (237). Four clones responsive to signals in a number of cell types appear to encode 1) a C2H2-type zinc finger DNA binding protein (225), 2) a protein related to the steroid receptor family of transcription factors (416), 3) a secreted protein (154) and 4) a protein whose structure is not defined by a structure/function category (120). Those clones that have been sequenced entirely are being examined with regard to 1) their possible required role in cell cycle progression and/or """"""""downstream"""""""" gene expression and 2) predicted function as assessed from conserved structural motifs in the translated protein sequence. In addition, we have begun defining upstream DNA elements in the 744 gene that regulate mitogen inducibility in T cells.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB009171-06
Application #
3813426
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code