INSIGHT: Pit-1/GHF-1: a pituitary-specific transcription factor linking general signaling pathways to cell-specific gene expression.

Abstract

Identification and ordering of the functional cellular components involved in transmitting a hormone signal from the cell membrane to the nuclear compartment have progressed quite rapidly in recent years. The availability of defined gene fragments ligated to reporter constructs has allowed investigators to map the critical promoter regions that mediate a particular hormone response. Using such minimally delimited hormone-responsive DNA elements in a variety of biochemical and recombinant DNA approaches, such as gel shifts and DNA ligand screening, the putative nuclear protein target(s) of specific hormone signaling pathways have been identified and their cDNAs cloned. Indeed, precisely these approaches were used to identify the CAMP-responsive DNA element (CRE: TGACGTCA) and to clone the nuclear factor [CAMP response element binding protein (CREB)], which together mediate many of the transcriptional responses of the PKA signaling pathway (for review, see Refs. 1 and 2). Although most of the CAMPregulated genes that were initially characterized contain a CRE, it became clear that other DNA motifs and nuclear factors (e.g. AP-2) distinct from the CRE and CREB, respectively, could also mediate the transcriptional effects of the cAMP/PKA pathway (1, 2). As if to validate the complexity by which the cAMP/PKA signal may be transduced, studies of two ancestrally related pituitary-specific genes, PRL (PRL) and GH (GH), have consistently implicated DNA binding sites for the POUhomeodomain protein, Pit-l/GHF-1 , as mediating the CAMP response (3-12). The results of Kapiloff et al. (13) which documented that Pit-l/GHF-1 was phosphorylated in vivo at Ser 115 and Thr 220 in response to CAMP or phorbol ester (TPA) treatment of GC rat