pll (Pelle) notes

UniProt Q05652 (KPEL_DROME), 501 aa; N-terminal death domain (55-121), C-terminal Ser/Thr kinase domain (213-499), catalytic K240.

Core biology (with provenance)

• Kinase: "pelle encodes a protein of 501 amino acids, the last 292 of which comprise a protein kinase catalytic domain" and "the kinase catalytic domain is required for biological activity" PMID:8440018.
• Autophosphorylation and phosphorylation of Toll: "We then demonstrate that Pelle can be autophosphorylated, and that this prevents binding to Toll as well as Tube." PMID:9806920
• Cactus kinase (IKK counterpart): "We conclude that Pelle acts as a Cactus kinase and preferentially phosphorylates Cactus at the serines required for signal responsiveness." and "In Drosophila, Toll signaling directs Cactus degradation via a sequence motif that is highly similar to that in IκBα, but without involvement of IKK." PMID:24086459
• Slimb link: "Pelle phosphorylates Cactus, triggering recognition by the Slimb βTrCP and subsequent ubiquitination and proteasome mediated degradation." PMID:24086459
• Death domain complex: "The interaction of the serine/threonine kinase Pelle and adaptor protein Tube through their N-terminal death domains leads to the nuclear translocation of the transcription factor Dorsal" PMID:10589682; "we find a heterotrimeric association of the death domains of MyD88, Tube, and the protein kinase Pelle" PMID:12351681.
• Membrane recruitment: "activated Toll induces a localized recruitment of Tube and Pelle to the plasma membrane" PMID:9609827.
• Immunity: "a dominant-negative version of the kinase Pelle can block induction of drosomycin by the cytokine Spaetzle, but does not affect induction of the antibacterial peptide attacin by lipopolysaccharide" PMID:10973475.
• Hippo link: "Cka was phosphorylated in vitro by wildtype Pll, but not the kinase-dead mutant Pll-K240R" PMID:26824654.
• Other substrates in vitro: dTRAF2 "is phosphorylated by Pelle in vitro" PMID:11447260.

Curation decisions

• GO:0004674 rows all ACCEPT; NEW GO:0008384 IkappaB kinase activity (IDA, PMID:24086459). Participation: Pelle catalyses Cactus phosphorylation. Comparator: IKK catalytic subunits (CHUK, IKBKB, fly IKKbeta) carry GO:0008384; Pelle is in the same enzymatic role for Cactus. GO:0008384 is_a GO:0004674 (OLS).
• Protein binding with Tube (several papers) -> MODIFY to GO:0070513 death domain binding; Pellino row REMOVE; Tehao row MODIFY to GO:0005121 Toll binding.
• IBA GO:0031663 LPS-mediated signaling REMOVE (fly LPS/attacin response is Pelle-independent; PMID:10973475). IBA nucleus MARK_AS_OVER_ANNOTATED.
• GO:0019221 cytokine-mediated signaling IBA ACCEPT (Spaetzle is a cytokine); GO:0008063 is not an is_a child of GO:0019221 in current GO (OLS parents: GO:0007166 only).
• GO:0007352 zygotic specification of D/V axis (PMID:6434989, a paper about maternal mRNA) -> MODIFY to GO:0009950; pll is a maternal-effect gene. QuickGO: only pll and dpp carry GO:0007352 in fly.
• Apoptotic process NAS REMOVE (death domain homology only).
• Hemocyte proliferation TAS (review, abstract-only) UNDECIDED.
• No GO:0002224 (TLR signaling) or PRR terms reach pll; GO:0008063 is used consistently.

Deep-research cross-check (2026-09-30)

Compared pll-deep-research-falcon.md with the review.
- Agrees: IRAK-family kinase; MyD88-Tube-Pelle death-domain complex; autophosphorylation; Pelle as the Cactus kinase standing in for IKK. The report's Cactus sites (Ser74/78/116, 75-80% reduction) and IkappaBalpha Ser32/Ser36 chimera were checked in PMID:24086459 ("mutating these three sites consistently reduced phosphorylation by 75-80%"), supporting the NEW GO:0008384 row.
- Minor conflicts, not acted on: domain boundaries (report: kinase ~130-501) differ from UniProt (213-499); review keeps UniProt. Report lists Dorsal as a candidate substrate; not established.
- Adds: Wu et al. 2015 (fetched, PMID:26474173, full text): Toll-independent anti-apoptotic role; "Pll physically interacts with and phosphorylates on dFoxO, which likely contributes to the cytoplasmic retention of dFoxO." Not in GOA; raised as a suggested question (negative regulation of apoptosis) rather than a NEW row. The apoptotic process NAS REMOVE stands: that row rested on death-domain homology, not on this paper. Zhang et al. 2024 (PMID:38292423): Tube/Pelle knockdown blocks Toll-1/Toll-7-induced autophagy in S2 cells; recorded as a reference only. Dillard et al. 2025 tumour work not checked; no change.
- Changes: references (+PMID:26474173, +PMID:38292423) and suggested_questions (+1). No annotation actions changed.