In addition, some tumors and their metastases seem to secrete and respond to such factors, establishing a dormant state when a large tumor is established. Understanding these factors and how they function might provide insight on ways to induce a dormant state in tumors and how to repress the proliferation of dormant metastases following surgical removal of a primary tumor. We found that the secreted proteins AprA and CfaD function as chalones in the social amoeba Dictyostelium discoideum. AprA, a protein with little similarity to known human proteins, and CfaD, a member of the conserved family of cathepsin L PD-161570 proteases are secreted by proliferating Dictyostelium cells and inhibit their proliferation. Cells lacking either AprA or CfaD proliferate more rapidly than wild-type cells and reach a higher stationary density. The addition of recombinant AprA or rCfaD slows the proliferation of cells. AprA shows saturable binding to cells, causes GTP uptake at the cell membrane, and requires the G proteins Ga8 and Gb for activity, suggesting that AprA signals through a G protein-coupled receptor. AprA and CfaD require each other for activity, and also require the kinase QkgA, the phosphatase CnrN and the putative transcription factor BzpN for activity. In addition to its proliferation-inhibiting activity, AprA, but not CfaD, acts as an autocrine chemorepellent that functions to Paroxetine hydrochloride hemihydrate disperse groups of cells that are at high density. This chemorepellent activity requires Ga8, QkgA, and CnrN but not BzpN, suggesting that AprA affects proliferation and cell movement through partially overlapping pathways. p21-activated kinases are a conserved family of kinases that bind to and are activated by small GTPases such as Rac and cdc42. PAKs function to regulate actin dynamics in processes such as bud growth in Saccharomyces cerevisiae, growth cone guidance in developing Drosophila neurons and chemotaxis towards cAMP in Dictyostelium. PAK1 induces the formation of filopodia and membrane ruffles in human fibroblasts, whereas Drosophila Pak3 inhibits lammelipodia formation in cell culture, indicating that PAKs can positively or negatively regulate actin-based structures.