An insulin/IGF-like signalling pathway in C. elegans plays a role in early development, the dauer/non-dauer decision, fertility and life span (1). Components of this pathway identified by genetic analysis include DAF-2, a homologue of the vertebrate insulin and IGF-I receptors, AGE- 1, a subunit of phosphoinositide 3-kinase (PI3K), DAF-18 (PTEN) phosphatase, PDK- 1(phosphoinositide-dependent kinase), AKT-1 and AKT-2 (protein kinase Bs) and DAF-16, a forkhead transcription factor. Mutations in
daf-2 or in
age-1 cause dauer larva arrest, and can double adult life (2-4). Although this signal transduction pathway between
daf-2 and
daf-16 has been well defined, several findings suggest the existence of a second
daf-2-
daf-16 pathway. For example, phenotypic analysis of 15
daf-2 mutants, which fall into two distinct classes, 1 and 2, suggested that the gene has two functional components,
daf-2A and
daf-2B (4). These potentially correspond to different signalling pathways emanating from
daf-2 into the cell. In addition, a gain-of-function allele of
akt-1(5), and the hypomorphic allele
daf-18(
e1375), fully suppress the dauer constitutive (Daf-c) phenotype of several severe
age-1 alleles yet only weakly suppress the relatively weak allele,
daf-2(
e1370). To investigate and characterise the putative second
daf-2 pathway, we have carried out interaction studies between several class 1 and class 2
daf-2 alleles and various components of the PI3K and other signalling pathways. Results of these interaction studies together with a revised model of
daf-2 signalling will be presented.