Short Stories
A “Firey” Pathway Response
(A Loose Analogy for Activation of the RTK Signal Transduction Pathway)
By Lauren Sawchyn
University of Maine
Ryan Tony Kevin (RTK: receptor tyrosine kinase), the only man on campus with three first names, is an odd fellow. Always concerned about alerting others to sudden emergencies, he sleeps with his bed half-way out his dorm-room door (RTK is a transmembrane protein), ready to pull the fire alarm. One bitter cold Maine evening, Ryan Tony Kevin smells smoke (a ligand) wafting up from the kitchen in his dorm.
RTK (receptor tyrosine kinase) detects smoke (the binding of a ligand) from the dorm kitchen.
“Holy diamonds and mother of pearl!” he cries. He is so shaken up by the possibility of burning alive, his whole persona changes and his hair turns white (conformational change in RTK); he reaches to pull the fire alarm!
RTK undergoes a conformational change to activated state.
The alarm causes a series of reactions (phosphorylations) to occur as the signal travels through the room’s wall (cell membrane) to the motherboard in the dorm basement (part of the cell interior).
The energy traveling through the electrical wires not only sets off a chain of alarms (phosphorylation reactions), but also causes the local police department (also in the cell interior) to be contacted.
RTK pulls the fire alarm which causes many electrical signals (phosphorylation reactions) to be sent through the dorm wall (cell membrane) to the motherboard (part of cell interior). This causes more alarms (phosphorylation reactions) to be set off and the police department (also in cell interior) to be contacted.
Dispatcher Alma Pieces (adaptor protein) of the police department recognizes the signal coming from Ryan Tony Kevin’s room (recognizes the phosphorylated tyrosines on RTK), and so she contacts (activates) the fire department chief, Gary “Not Real” Presley (GNRP: guanine nucleotide releasing protein), who then calls (activates) his off-duty (inactive) partner, Rastaman G (Ras G protein), who is out walking his Good Dog Pete (GDP).
Startled by the phone, Good Dog Pete pulls hard on his leash (is phosphorylated to GTP), pulling Rastaman G into action.
Rastaman answers his cell phone, and then calls (activates) fellow volunteer fire fighter, Prof. King Crab (PKC: protein kinase C), of the Marine Biology department, meanwhile asking a GAP (GTPase-activating protein) employee in the town’s shopping center to hold Good Dog Pete for a moment.
Once Prof. King Crab gets the message, the GAP employee, having calmed the dog (hydrolyzed GTP back to GDP), hands the dog back to Rastaman G, and Rastaman G, seeing his Good Dog Pete (GDP) calm and happy, goes back to his stroll (inactive state).
Prof. King Crab (PKC: protein kinase C) contacts (phosphorolates) many individuals (kinases), including his friend Raf (Raf protein), the local emergency technician, who upon receiving the message, calls and wakes up (activates by phosphorylation) his partner, Mr. E. Killer (MEK protein)
Mr. E. Killer, wanting the students to be aware of what is going on, calls (activates by phosphorylation) Erik (ERK protein) the Resident Assistant. Erik is responsible for relaying the message to (phosphorylating) the group of students (transcription factors) waiting outside (in the nucleus).
MEK signals Erik (ERK), the resident assistant.
So, Erik goes outside (enters the nucleus) and relays the message.
As the student group begins to understand what has happened (become phosphorylated), they relay the message to other groups (genes), causing a general expression of alarm and eventual action (gene transcription and translation).
Eventually, the whole campus (cell) knows what has happened, and actions are taken to take care of the situation.
Fortunately, no one was hurt from the explosion in the kitchen caused by someone carelessly leaving the dorm stove on.
ERK relays the message to the group of students (transcription factors) waiting outside (in the nucleus).
Students relay the message to others (the genes), which causes expression of alarm and eventual action (gene transcription and translation).
Ryan Tony Kevin (RTK: receptor tyrosine kinase) calms back down (returns to inactive state), and his hair turns back to its normal shade.
Satisfied with a job well done, he climbs back into bed and goes to sleep, ready to act when the next big event comes around.
Why is this pathway important?
The RTK pathway can activate cell division and ensure proper differentiation of cells by facilitating gene expression. The ligands that attach to and activate the transmembrane receptors (RTKs: receptor tyrosine kinases) in the RTK pathway can be fibroblast growth factors, epidermal growth factors, platelet-derived growth factors, and stem cell factors.
The Ras protein, that plays an important role in the RTK pathway, is integral to its control over cell division. Mutations that cause defects in the Ras protein, leaving Ras in its active state unable to return to its inactive state, are responsible for a large proportion of human tumors. With Ras constantly in its active state, the cell does not receive the message to stop dividing.