This application seeks partial funding for a new Gordon Research conference on Signal Transduction within the Nucleus to be held February 6-11, 2005 at the Rancho Santa Barbara Marriott, Buellton, California. The funds requested will be used exclusively to support the conference and travel expenses of junior investigators who will be attending the conference and presenting their work as invited presentations, short talks or posters. The broad goal of this conference is to provide a form for review and discussion of recent research on the emerging field of nuclear signaling. This field centers on the novel concept that, similar to the agonist-induced metabolism at the plasma membrane, agonist stimulation leads to the generation of second messengers at and within the nucleus that leads to the production of nuclear localized second messengers. The mechanisms involved in regulating the generation and metabolism of these second messengers, and their precise physiological roles, are part of a complex picture that involves many enzymes and regulatory molecules. This conference brings together a wide variety of investigators focused on understanding the agonist-induced modulation of these components. Some of the principal enzymes include phosphoinositide-specific phospholipase Cs, phosphatidylinositol 3-kinases, phosphatidylcholine-specific phospholipase Cs, phospholipase A2s, lipoxygenases, cyclooxygenases, sphingomyelinases and glycosylating enzymes. These enzymes modulate the levels of key signaling molecules such as diacylglycerol, inositol phosphates, D-3 phosphonylated phosphoinositides, arachidonic acid and related eicosanoid, glycoproteins, glycolipids and sphingolipids. To address important physiological roles, other topics will include nuclear events that are regulated by the nuclear signaling pathways such as chromatin remodeling, transcription and RNA transport. Additional topics focus on how these pathways contribute to disease processes. The requested funds will be invaluable to the support of this conference.