The PKCalpha-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals

Related Experiment Video

Updated: Aug 17, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
05:39

Spontaneous Murine Model of Anaplastic Thyroid Cancer

Published on: February 3, 2023

Yimin Zhu1, Qihan Dong, Bee Jen Tan

  • 1Department of Biochemistry, Faculty of Science, The National University of Singapore, Singapore, Singapore.

Cancer Research
|June 3, 2005
PubMed

Insights

A mutation in Protein Kinase C alpha (PKCalpha) impairs its membrane binding, leading to a loss of its tumor-suppressing functions. This suggests targeting wild-type PKCalpha could treat endocrine tumors.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Protein Kinase C (PKC) regulates cell growth and is a cancer therapy target.
  • A PKCalpha D294G mutation is linked to invasive endocrine tumors.
  • The underlying mechanism of this mutation's role in tumorigenesis was unclear.

Purpose of the Study:

  • To investigate the biochemical and cell biological consequences of the PKCalpha-D294G mutation.
  • To determine if the mutant PKCalpha exhibits altered membrane binding and signaling capabilities.
  • To elucidate the functional role of wild-type PKCalpha in endocrine tumor progression.

Main Methods:

  • Assessed membrane binding of wild-type and mutant PKCalpha after phorbol ester treatment.
  • Evaluated the translocation of myristoylated alanine-rich protein kinase C substrate (MARCKS).
  • Measured mitogen-activated protein kinase activation and melatonin-stimulated neurite outgrowth.

Main Results:

  • PKCalpha-D294G translocated to membranes but exhibited impaired tight membrane binding.
  • The mutant failed to transduce key antitumorigenic signals, including MARCKS translocation and MAPK activation.
  • Melatonin-stimulated neurite outgrowth was not augmented by the mutant PKCalpha.

Conclusions:

  • The PKCalpha-D294G mutation represents a loss-of-function, compromising its antitumorigenic activities.
  • Wild-type PKCalpha likely plays a protective role against endocrine tumor progression.
  • Selective activators of PKCalpha may offer novel therapeutic strategies for endocrine tumors.

More Related Videos

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells09:37

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells

Published on: August 25, 2021

Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation07:13

Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation

Published on: March 14, 2017

Related Concept Videos

Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
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 rapamycin-insensitive companion...
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...
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...