Identification and functional analysis of a developmentally regulated extracellular signal-regulated kinase gene in Dictyostelium discoideum.

Abstract

We have cloned a developmentally regulated mitogen-activated protein kinase (extracellular signal-regulated kinase) from Dictyostelium discoideum designated ERK1. Using anti-pTyr antibodies, we show that ERKI is phosphorylated on tyrosine in vivo and that it will phosphorylate myelin basic protein. The (16,26). As the aggregate forms, extracellular signals produced within the organism induce cell type differentiation and regulate morphogenesis. These events lead to the production of a migrating slug followed by culmination and the generation of a mature fruiting body containing spores and stalk cells (49,50,80). Biochemical and molecular genetic analyses over the last few years have identified components required for various aspects of these processes and have led to a further understanding of the regulatory pathways controlling development. Genes encoding membrane receptors, coupled GP and Got subunits, the effectors adenylyl cyclase and phospholipase C, and the transcription factor GBF have been cloned and analyzed at a molecular level (12,17,32,65,72,81,82 the membrane to those in the nucleus is cAMP-dependent protein kinase (PKA). PKA has been shown to be essential for aggregation, cell-type-specific expression of the ecmB gene, the induction of prespore cell differentiation, and the induction of sporulation and spore cell-specific gene expression (1, 27, 35, 36, 40, 56-58, 76, 77 (8, 21-23, 61, 79, 84). In metazoans, both G protein-and tyrosine kinase-coupled receptors regulate growth responses, gene expression, and cellular differentiation via MAPK-containing pathways (2,7,11,51,60,64,83). MAPK family members have also been shown to directly phosphorylate transcription factors in mammalian cells, including Myc, Elk, and Jun proteins, leading to an increase in the rate of transcription (14,29,38,46,59,74,75).

Multiple Roles of the Novel Protein Tyrosine Phosphatase PTP3 during Dictyostelium Growth and Development

“…6A). A similar observation has also been made for PTP2, ERK1, rasD, and G␣1 (11,15,18,27) (see Discussion). At the mound stage (9 h; Fig.…”

Extracellular polyphosphate signals through Ras and Akt to prime Dictyostelium discoideum cells for development

“…Cells lacking RasC (Daniel et al, 1994), the p21-activated kinase PakD (Garcia et al, 2014), Erk1 (also known as ErkA) (Gaskins et al, 1994), the Dictyostelium Akt homologs Pkba and PkgB (Meili et al, 1999(Meili et al, , 2000, and the suppressor of cAMP receptor (SCAR) component NapA (Ibarra et al, 2006) were all nonresponsive to polyphosphate-induced development (Table 3). Cells lacking the secreted factor CtnA (Brock and Gomer, 1999), the frizzled-like receptors FslB and FslK (Prabhu and Eichinger, 2006), the inositol hexakisphosphate kinase I6kA (Luo et al, 2003), the G-protein coupled receptors GrlB, GrlE and GrlH (Prabhu and Eichinger, 2006) the autocrine factor CfaD (Bakthavatsalam et al, 2008), the target of rapamycin complex 2 (TORC2) component Lst8 (Lee et al, 2005), the Dictyostelium polyphosphate kinase Ppk1 (Livermore et al, 2016), and the PTEN homolog CnrN (Tang and Gomer, 2008) did form aggregates in response to polyphosphate (Table 3).…”

“…The cells used were Dictyostelium wild-type Ax2, pakD − (DBS0350281) (Garcia et al, 2014), erk1 − (DBS0350622) (Gaskins et al, 1994), pkbA − (DBS0349876) (Meili et al, 1999), pkbA − /pkgB − (DBS0236785) (Meili et al, 2000), rasC − (DBS0236853) (Daniel et al, 1994), napA − (DBS0236596) (Ibarra et al, 2006), adrm1 − (DBS0238203) (Cherix et al, 2006), fslB − (DBS0350230) (Prabhu and Eichinger, 2006), fslK − (DBS0350229) (Prabhu and Eichinger, 2006), ctnA − (DBS0235624) (Brock and Gomer, 1999), i6kA − (DBS0236426) (Luo et al, 2003), grlB − (DBS0350074) (Prabhu and Eichinger, 2006), grlE − (DBS0350075) (Prabhu and Eichinger, 2006), grlH − (DBS0350226) (Prabhu and Eichinger, 2006), cfaD − (DBS0302444) (Bakthavatsalam et al, 2008), lst8 − (DBS0236517) (Lee et al, 2005), ppk1 − (DBS0350685) (Livermore et al, 2016) and cnrN − (DBS0302655) (Tang and Gomer, 2008). Mutant genotypes were verified by PCR, and cells were kept under constant selection.…”

Activation of the Mitogen-activated Protein Kinase ERK2 by the Chemoattractant Folic Acid in Dictyostelium

“…Two MAP kinases, ERK1 and ERK2, have been identified and their functions characterized. ERK1 is required for vegetative growth and is thought to play roles during multicellular development (15), while ERK2 is required for the activation of adenylyl cyclase by the chemoattractant cAMP during aggregation, prespore-specific gene expression, and morphogenesis (2,16). erk2 null cells are aggregation-deficient due to the inability to activate adenylyl cyclase and relay the cAMP signal but show normal activation of guanylyl cyclase, which couples to chemotaxis (17).…”