Cell Signaling Overview

Overview

This section explains how cells respond to signals through signaling pathways, affecting gene expression, cellular metabolism, cell growth, and programmed cell death (apoptosis).

Gene Expression via Signaling Pathways

• Some signaling pathways regulate gene expression by controlling RNA transcription and protein translation.
• The MAPK/ERK pathway transmits signals from the cell surface receptor to the nucleus to regulate protein synthesis.
• Activated ERK kinase phosphorylates MNK1, which phosphorylates eIF-4E, allowing mRNA to unfold and initiate protein synthesis.
• PKC phosphorylates the inhibitor I-κB, releasing NF-κB so it can enter the nucleus and activate transcription.

Cellular Metabolism Changes

• Adrenaline activates β-adrenergic receptors in muscle cells, increasing cyclic AMP (cAMP) levels.
• cAMP activates PKA, which phosphorylates enzymes that promote glycogen breakdown and inhibit glycogen formation.
• This provides glucose for muscle use during a fight or flight response.

Cell Growth and Cancer

• Growth factors bind to receptor tyrosine kinases (RTKs), activating RAS and the MAP kinase pathway to promote cell division.
• Mutations in signaling proteins such as RAS can lead to uncontrolled cell division and cancer.
• Oncogenes are genes with the potential to cause cancer due to mutations affecting signaling pathways.
• HER2 overexpression in breast cancer can be targeted by the drug Herceptin, which reduces abnormal cell signaling.

Programmed Cell Death (Apoptosis)

• Apoptosis is a controlled process by which damaged or excess cells self-destruct to prevent harm to the organism.
• Apoptosis can be triggered internally (cell health checkpoints) or externally (loss of extracellular matrix contact).
• During immune development, T-cells that recognize self-proteins are removed by apoptosis to prevent autoimmune reactions.
• Apoptosis shapes tissues during embryonic development, such as removing tissue between developing fingers and toes.

Termination of Signal Cascade

• Signal cascades must be terminated to prevent overactive responses, such as in cancer.
• Ligand removal or degradation stops signaling at the receptor level.
• Enzymes like phosphatases reverse phosphorylation, and phosphodiesterase degrades cAMP.
• Calcium pumps restore normal ion concentrations after signaling events.

Key Terms & Definitions

• MAPK/ERK pathway — A chain of proteins that transmits cell surface signals to the nucleus for gene expression.
• PKC (Protein Kinase C) — A kinase that phosphorylates proteins to regulate cellular functions.
• NF-κB — A transcription factor activated by release from inhibitor I-κB, controlling immune and inflammatory responses.
• cAMP — Cyclic AMP, a second messenger involved in many signaling pathways.
• PKA — Protein kinase A, activated by cAMP, regulates metabolism via phosphorylation.
• Oncogene — A gene with the potential to cause cancer when mutated or overexpressed.
• Apoptosis — Programmed cell death, a normal cellular self-destruction process.
• Phosphatase — An enzyme that removes phosphate groups to reverse phosphorylation.

Action Items / Next Steps

• Review figures 9.10 and 9.14 for visual understanding of ERK signaling and protein translation regulation.
• Study the roles of kinases and phosphatases in signal termination.
• Prepare for questions on the roles of apoptosis in development and immune system function.