Mitogen-Activated Protein Kinase 1 (MAPK1)

Overview

MAPK1 encodes mitogen-activated protein kinase 1, also known as ERK2, a serine/threonine kinase in the MAPK/ERK signaling cascade. This pathway transduces extracellular growth and stress signals from upstream regulators such as RAF and MEK to downstream effectors that control proliferation, differentiation, survival, migration, and metabolic adaptation. Because of its central position in signal transduction, MAPK1 is frequently evaluated in cancer biology and other disease contexts as a readout of pathway activation, typically through its phosphorylated form, phosphorylated ERK.

In biomedical research, MAPK1 is often studied alongside related signaling nodes including KRAS, FLT3, Akt1, STAT5A, vascular endothelial growth factor A (VEGFA), and ESR1, reflecting its role in broader oncogenic and tissue-response networks. Recent studies have used MAPK1 as a mechanistic marker of pathway inhibition, a docking target in computational screening, and a candidate gene in regulatory analyses such as microRNA-target prediction. These investigations collectively reinforce MAPK1 as a key mediator of MAPK/ERK signaling in cancer, metabolic disease, and regenerative biology.

Recent Publications Summary

Recent publications have continued to implicate MAPK1 as a recurring node in cancer-related signaling and natural-product target prediction. In hepatocellular carcinoma, network pharmacology and molecular docking identified MAPK1 among several key candidate targets for a urolithin derivative with antiproliferative, anti-migratory, cell-cycle arrest, and pro-apoptotic effects; the authors proposed involvement of the PI3K/Akt and MAPK signaling pathways, with molecular dynamics supporting protein-ligand stability 41855633Mar. Similarly, a multi-omics study of Heuchera micrantha metabolites used network pharmacology and docking to predict that selected dipeptides may interact with MAPK1, EGFR, and SRC in cancer- and inflammation-related pathways, although these interactions were explicitly described as requiring experimental validation 42425198Jul.

MAPK1 also appeared in studies of broader pathway modulation by natural products and traditional medicines. In a protocol for evaluating metformin for pain, the authors noted that proposed analgesic mechanisms may include inhibition of mitogen-activated protein kinase signaling downstream of AMP-activated protein kinase activation, reflecting a possible link to MAPK1-associated nociceptive sensitization pathways 42468965Jul. In a preclinical study of modified Suoquan Wan for overactive bladder, the investigators reported benefit through the Piezo1/MAPK/MLC axis in rats, indicating modulation of MAPK signaling as part of the therapeutic effect, though the abstract did not isolate MAPK1 specifically 41905730Mar.

Across oncology-focused pharmacology, MAPK1 was also identified as a docking target for chemically diverse agents. DOTP, a phthalate alternative, was computationally predicted to bind MAPK1 among six high-affinity carcinogenic targets, and experimental work showed that DOTP exposure promoted tumor-cell proliferation and increased PTPN11 and ESR1 protein levels in a concentration-dependent manner 41780785Mar. In addition, a study of SHP2 allosteric inhibition reported that the preclinical candidate I-0436650 strongly inhibited ERK phosphorylation in cells and suppressed growth of EGFR- and RAS-dependent cell lines, supporting vertical inhibition of the RAS-RAF-mitogen-activated protein kinase pathway in RAS-driven Cancers 42593923Aug.

MAPK1 was also included in a study of exosomal miR-106b-5p in osteoporosis, where the microRNA was reported to target SMAD5, BMP2, and MAPK1 genes 42049413Apr. Although the abstract did not provide mechanistic detail for MAPK1 beyond target nomination, it supports continued interest in MAPK1 across both cancer and bone-related disease contexts.

What Changes, What Holds

1. MAPK1 remains a recurrent target in cancer pharmacology, but these studies add only candidate-level support
REINFORCES MAPK1 continues to be treated as a plausible node in anti-cancer network pharmacology and docking screens, matching the Overview’s description of it as a common mechanistic marker and docking target. The new work does not establish a new biological role or overturn the MAPK/ERK account; it mainly extends the list of compounds proposed to act through MAPK1, while leaving the experimental status of those interactions uncertain and, in one case, explicitly unvalidated. 41855633Mar42425198Jul

2. MAPK signaling is being invoked in broader therapeutic contexts beyond oncology
NEW DIRECTION metformin-related analgesic hypotheses and the overactive-bladder study point to MAPK pathway modulation as part of pain and urinary-tract biology, a role not covered in the Overview’s cancer, metabolic disease, and regenerative framing. The first is still a protocol-level mechanism proposal, and the second does not isolate MAPK1 specifically, so neither changes the settled account of MAPK1 itself; together they suggest a wider set of disease contexts in which MAPK signaling is now being considered. 42468965Jul41905730Mar

3. MAPK1 remains a vertical-inhibition readout and docking target in oncogenic signaling studies
REINFORCES DOTP’s predicted binding to MAPK1 and the ERK-phosphorylation suppression seen with SHP2 allosteric inhibition both fit the established view of MAPK1 as a downstream indicator and intervention point in the RAF/MEK/ERK cascade. The added value here is not a new function for MAPK1, but another illustration that pathway-directed perturbations in RAS- and EGFR-driven cancer settings are still being interpreted through ERK/MAPK1 activity. 41780785Mar42593923Aug

4. MAPK1 is now being nominated as a microRNA target in bone disease, not just cancer biology
NEW DIRECTION Exosomal miR-106b-5p targeting MAPK1 in osteoporosis broadens the baseline account, which emphasized cancer, metabolic disease, and regenerative biology but did not name bone pathology or microRNA-mediated regulation in that setting. The evidence is only target nomination, so it does not yet establish mechanism; still, it marks MAPK1 as a candidate node in skeletal disease networks and shows that its research footprint is widening beyond the Overview’s main examples. 42049413Apr

Overview update candidates: MAPK1 as a candidate node in pain-related MAPK signaling; MAPK1 as a nominated microRNA target in osteoporosis.