Seminar with researchers at UIC: Akt/PI 3-Kinase Signaling in Cell Death and Cell Survival

Last week, a colleague and I had the pleasure of attending a seminar for researchers at The University of Illinois at Chicago. The talk was given by Chandra Mohan, PhD of EMD Millipore Biosciences on the topic “Akt/PI 3-Kinase Signaling in Cell Death and Cell Survival.”

As Dr. Mohan said, “Akt (protein kinase B) has emerged as a critical enzyme in signal transduction pathways involved in cell proliferation, apoptosis, angiogenesis, and diabetes.”  The principal role of Akt is to facilitate growth factor-mediated cell survival and to block apoptotic cell death, he said.

“A number of oncogenes and tumor suppressor genes that function upstream of Akt influence cancer progression by regulating Akt. Akta is expressed to various degrees in breast cancer cell lines and is important in estrogen-stimulated growth. Treatment of multiple myeloma cell lines with the Akt inhibitor, 1L-6-Hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, results in reduced survival of both drug resistant and drug sensitive cells,” he presented.

“Akt plays a critical role in tumorigenesis, becoming activated when tumor suppressors such as p27 and PTEN lose their functions. Phosphorylation of p27 at Thr157 by Akt impairs its nuclear import. Cytoplasmic mislocalization of p27 has been strongly linked to loss of differentiation and poor outcome in breast cancer,” he said.  “Akt is also reported to physically associate with endogenous p21, a cell cycle inhibitor, and phosphorylate it at Thr145, causing its localization to the cytoplasm and subsequent degradation.”

Akt and p53 play opposing roles in signaling pathways that determine cell survival – and the interaction between these two molecules is becoming an important area of study.

In addition to the presentation, Dr. Mohan offered copies of his book, Signal Transduction: A Short Overview of its Role in Health and Disease.

Who are the researchers and why are they studying Signal Transduction?

1.    Diabetes and other metabolic disorders

• To elucidate the mechanism of binding and action of insulin and identify the causative factors in the development of diabetes. Also, identify the intracellular sites of insulin action.
• Product categories: hormones, protein kinases, protein phosphatases activators and inhibitors, cyclic AMP and GMP related products, calcium channel modulators

2.    Cancer

• To identify how and why certain cells respond abnormally to environmental signals and then design and develop new therapeutic measures to prevent and treat cancer in its earliest stage.
• Product categories: protein kinases, MAP kinase inhibitors, phosphatase inhibitors and activators, phorbol esters, nitric oxide related products, GTP-binding proteins, farnesyltransferase inhibitors, tyrosine kinase inhibitors, calmodulin related products

3.    Apoptosis, programmed cell death

• A failure of cancer cells to die. The interest in this field has been growing rapidly also in relation to Alzheimer’s disease where too many neurons die prematurely.
• Product categories: caspase inhibitors and substrates, proteasome inhibitors, inhibitors and inducers of apoptosis, reagents for cell cycling

4.   Hypertension and other cardiovascular disorders

• Design new treatments to reduce the incidence of hypertension, angina, and the risk of stroke and related complication
• Product categories: calcium channel modulators, nitric oxide related products, calcium probes, ionophores

5.   Osteoporosis and mineral metabolism

• To elucidate the mechanisms involved in bone growth and in increased mineral loss. Design and develop appropriate therapies for prevention of osteoporosis
• Product categories: growth factors, cytokines, calcium probes, second messengers, protein kinases

6.   Infection, trauma, and sepsis

• Design and develop new treatments to prevent and treat infection and sepsis. Help in the wound healing process.
• Product categories: cytokines, growth factors, protein kinases, calcium modulators, oxidative stress tools

7.   Neuroscience

• To identify the mechanisms involved in the development of Alzheimer's disease, neurochemical complications in muscular dystrophy, mental disorders, neuritis, and abnormalities in neuronal development, and design appropriate therapies.
• Product categories: regulators of calcium metabolism, neurotoxins, nitric oxide related products, protein kinases and related products, calmodulin and related products

Click here for more information about this research – along with a request form for the book.