Molecular Insights of MAP4K4 Signaling in Inflammatory and Malignant Diseases

Sunil Kumar Singh1, Ruchi Roy2, Sandeep Kumar1,3

  • 1Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL 60612, USA.

Cancers
|May 16, 2023
PubMed

Insights

Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) signaling is vital in cell functions and diseases. This review explores MAP4K4

Area of Science:

  • Cellular signaling pathways
  • Molecular biology
  • Cancer research

Background:

  • Mitogen-activated protein kinase (MAPK) cascades are central to cellular signal transduction.
  • MAPK pathways involve sequential kinase activations: MAP3K, MAP2K, and MAPK.
  • MAP4K4, a MAP kinase kinase kinase kinase, activates MAP3K and influences cellular processes.

Purpose of the Study:

  • To review the multifaceted role of MAP4K4 in diseases.
  • To examine MAP4K4's involvement in cancer-associated cachexia.
  • To explore MAP4K4 as a potential target for novel therapies.

Main Methods:

  • Literature review of studies on MAP4K4 signaling.
  • Analysis of MAP4K4's function in various cellular responses.
  • Investigation of MAP4K4's role in both malignant and non-malignant conditions.

Main Results:

  • MAP4K4 is implicated in cell proliferation, transformation, migration, and inflammation.
  • Overexpression of MAP4K4 is common in glioblastoma, colon, prostate, and pancreatic cancers.
  • MAP4K4 contributes to cancer-associated cachexia and has a pro-survival role in malignancies.

Conclusions:

  • MAP4K4 is a significant mediator in diverse diseases, including cancer.
  • Understanding MAP4K4's functions is crucial for developing targeted therapeutic strategies.
  • MAP4K4 presents a promising target for future cancer treatments and cachexia management.

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.7K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.0K
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.4K