The Protein Kinase YakA Regulates G-protein-linked Signaling Responses during Growth and Development of Dictyostelium

Abstract

A genetic screen for Dictyostelium mutants that phenotypically resemble cells lacking the G-protein β-subunit yielded the protein kinase YakA. Like β-null cells, yakA-null cells fail to enter development and display slow growth on bacterial lawns. We created a temperature-sensitive yakaA mutant and showed that YakA activity is required not only at the onset but also during development. The yakA-null cells have strong defects in folic acid-induced responses, such as actin polymerization and cGMP accumulation, indicating that they play a role in G-protein-mediated signaling responses. We propose that YakA acts downstream of G-proteins, because cAMP receptors still couple to G-proteins in the yakA mutant. In addition, the previously observed growth arrest induced by overexpression of YakA also occurs in gβ mutants. We localized YakA-GFP to the cytosol suggesting that YakA may be a functional homolog of its mammalian counterparts Dyrk2 and Dyrk3, a subclass of dual-specificity Yak-related kinases (Dyrk) with unknown function.