Riva Shirol12573630

KINASE-LINKED RECEPTORS: SIGNALLING MOLECULE PLUS RECEPTOR EQUALS EFFECT - WITH SOME EXTRA STEPS

What is a Kinase – Linked receptor?Kinase linked receptor are transmembrane receptors which means they span the entire cell membrane and have molecules on the outside and inside of the cell. These receptors are activated when a ligand or a signalling molecule binds to the receptor region, AKA, the N-terminus it causes a chain reaction intracellular leading to a host of different outcomes https://www.nature.com/scitable/topicpage/rtk-14050230. Tyrosine attached to the intracellular component of the receptor is, AKA the C-terminus, which gets phosphorylated by ATP (commonly referred to as ‘cell energy currency’), which donates a phosphate group to the Tyrosine, activating it. Tyrosine then goes on to activate reply proteins, which then causes cell proliferation, and differentiation.

Essentially this process involves a signalling molecule and receptor, which bind together and activate pathways which result in protein synthesis and cell generation or reproduction.

Lets break this down even further. Think of this as a puzzle, where 1 piece connects to another and another and another and finally you see the bigger picture.

As complicated this process seems, it can be broken down in 4 simple steps:

1. Ligand binds to receptorSignalling molecule comes and binds to the receptor on the surface of the cell

2. Two receptors bind together to form a dimer Two activated receptors join together and form what is called a dimer (2 units joined together) https://www.nature.com/scitable/topicpage/rtk-14050230

3. Phosphorylation ATP (cells energy currency) donates a phosphate group to Tyrosine resulting in activation

4. Relay proteins are activated and cause cellular response

Inactive replay proteins are activated, generating different responses such as, production of different proteins and cell proliferation (growth and reproduction)

http://bio1151.nicerweb.com/Locked/media/ch11/Tyrosine.html

Riva Shirol12573630

Types of Kinase – linked receptorsNow that we’ve talked about what they are and how they work, lets take a look at some examples of the receptors and what these are responsible for. The first example is growth factors, e.g. Epidermal growth factor (EGF) receptors. Epidermal cells are cells that cover all the internal and external surfaces of the body. Growth factor molecules activate growth factor receptors when they are bound to them and result in enhancement of maturation of the cell and lead to cell differentiation. The receptors are also present on the surface of neurons within the cerebral and cerebellum of the brain and on other cells of the central nervous system (CNS). https://www.ncbi.nlm.nih.gov/pubmed/15110798

Another example of Kinase- linked receptor is Insulin receptor. Insulin is a hormone, which is released by the pancreases, and plays the crucial role in glucose metabolism. https://www.ncbi.nlm.nih.gov/books/NBK378978/Fun fact: Insulin receptors exist as dimers and while others are lone receptors and need to be activated in order to form dimers. When these receptors are activated by the hormone Insulin, it causes downstream effects with activate metabolic function of Insulin. These effects include lowering the glucose concentrations within the blood by storing it in liver and fat cells and allowing glucose to travel into cells so that it may be used to produce energy in the form of ATP. https://www.ncbi.nlm.nih.gov/pubmed/2534271

The last example of Kinase – linked receptors we will explore are Platelet derived growth factor (PDGF). Platelets are cells that circulate in blood plasma which enable clotting when a broken blood vessel or cut or is detected https://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/centers_excellence/womens_cardiovascular_health_center/patient_information/health_topics/platelets.html. There are 2 types of PDGF receptors, PDGF – alpha and PDGF – beta. Both subtypes of receptor when activated by their growth factors inhibit or promote embryonic development, formation of blood vessels and cell proliferation. https://www.sinobiological.com/Platelet-derived-Growth-Factor-PDGF-Receptors-a-6628.html

3 most common examples of Kinase linked receptors, with their general structure and subunits identified. The image also shows how Insulin receptors exist as dimers and the other 2 exist as single unit receptors. http://namrataheda.blogspot.com.au/2013/02/types-of-receptors-part-2.html

HER-2 - and Trastuzumab Lets see if you can keep up. Human epidermal growth factor receptor 2 (HER – 2) is a kinase- linked receptor expressed on healthy breast cells, about 2000 receptors expressed per cell. These receptors when activated lead to gene expression and cell proliferation.

When too many of these receptors are expressed, stimulation can lead to uncontrolled cell growth resulting in tumors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3092522/.

Interesting fact: 1 in 5 breast cancers are a result of over expression of HER2 https://www.mayoclinic.org/breast-cancer/expert-answers/faq-20058066

But here’s the good news, a drug called Trastuzumab or Herceptin, which contains antibodies that attach and block the HER-2 receptors, prevent signaling molecules from attaching and stimulating it, thus preventing the cell from maturing and uncontrollably proliferating, destroyed the cancer tissue https://canceraustralia.gov.au/affected-cancer/cancer-types/breast-cancer/treatment/what-does-treatment-breast-cancer-involve/targeted-therapies/types-targeted-therapy/trastuzumab-herceptin

Riva Shirol12573630

References

Images