gskA (GSK-3, P51136) – Dictyostelium discoideum – curation notes

Deep research status

just deep-research-falcon DICDI gskA --fallback perplexity-lite was run (2026-10-05) and
failed: Falcon (Edison API) returned 402 Payment Required, and the perplexity-lite
fallback was not available ("'perplexity' not available. Available: openai, falcon,
openscientist"). No deep-research file was produced. The review is therefore based on
the cached publications (16 PMIDs, just fetch-gene-pmids DICDI gskA) and the UniProt record.

Full text available: 11032815, 20534815, 21205787, 22020250, 23135995, 23787121,
24653039, 31263268. Abstract-only: 7813009, 10571182, 15342480, 15366765, 22944283,
27237792, 29626371; 9784196 has no abstract text at all.

Identity

• Single GSK-3 gene in Dictyostelium; 467 aa CMGC Ser/Thr kinase, GSK-3 subfamily (UniProt).
• "Dictyostelium possesses only a single GSK-3 gene that can be deleted to eliminate all
  GSK-3 activity" PMID:23787121.
• Lithium-inhibited; Mg2+ cofactor (UniProt). Kinase-dead GskA(K85R) fails to rescue the
  null PMID:20534815.

Upstream regulation

• Activated downstream of cAMP receptor cAR3 via tyrosine kinases ZAK1 and ZAK2
  PMID:10571182
  PMID:21205787.
• LKB1 acts upstream; lkb1 knockdown lowers GSK3 activity PMID:22020250.

Cell-fate (prespore vs prestalk B) – classic role

• Null mutant: few spores, excess stalk/pstB cells; cAMP fails to inhibit pstB and to induce
  prespore differentiation PMID:7813009.
• Ax2/gskA- strain: accelerated early development, curtailed slug migration, DIF-1
  hypersensitivity, ectopic ecmB PMID:15342480.
• Cell-type specific regulation by ZAK1 (pstB, autonomous) and ZAK2 (prespore)
  PMID:21205787.

Substrates / direct kinase function

• Dd-STATa: serine phosphorylation by GskA enhances nuclear export PMID:11032815.
• TacA: nuclear export partially GskA dependent PMID:22944283.
• GtaC (GATA TF): GskA required for cAMP-induced mobility shift; purified Flag-GskA restores
  shift in vitro PMID:24653039.
• DydA (Daydreamer, MRL adaptor) PMID:23135995; GflB (RapGEF) PMID:27237792;
  PdeD, dynacortin, SogA PMID:29626371; RacE (Rho) Ser192 → mTORC2 activation
  PMID:31263268. Note: in 23135995 and 31263268
  the in vitro phosphorylation used recombinant human GSK-3beta; in-cell dependence used
  gskA- cells or GSK-3 inhibitors.

Chemotaxis / signaling

• gskA- cells chemotax poorly to cAMP and folate, fail to activate PIP3 and TORC2 signalling
  PMID:20534815.
• Kolsch et al. 2013: Ras kinetics misregulated in gskA-, extended PI3K recruitment and
  PKB/PKBR1 phosphorylation, reduced MyoII assembly PMID:23135995. This conflicts in part
  with Teo 2010 (reduced TORC2/PKB activation); the Senoo 2019 mechanism supports a positive
  role toward mTORC2.
• Polarization toward cAMP depends on ZAK1 phosphorylation of GSK3 PMID:21205787.

Mitosis

• GskA-GFP on central spindle and centrosomes; null fails to elongate spindle, cytokinesis
  defect in suspension, no chromosome segregation defect PMID:23787121.

Curation decisions (summary)

• GTPase regulator activity (IDA, PMID:23135995): REMOVE – full text read; the evidence is
  altered Ras-GTP kinetics in gskA- cells (indirect), GskA is a kinase not a GTPase regulator.
• tau-protein kinase activity (IEA from EC 2.7.11.26): over-annotation; no tau in Dictyostelium.
• TOR signaling (IMP): MODIFY to positive regulation of TORC2 signaling.
• cell differentiation (IMP, 7813009): MODIFY to positive regulation of sorocarp spore cell
  differentiation / negative regulation of sorocarp stalk cell differentiation.
• regulation of cell adhesion (TAS, review 15366765, abstract-only, does not mention GSK3):
  UNDECIDED.