Cell Signaling

Why did it take so long for multicellular organisms to develop?

complex, specialized functions had to develop over time

• atmospheric condtions/more oxygen needed

signal transduction

process of cells responding to extracellular signals

signaling cell sends extracellular signal molecule

detected by receptors in target cell

extracellular signal molecules

molecules outside the cell that cause an intercellular response when bound to a receptor

hormones

extracellular signals that are secreted or transported by blood/sap to target tissue

endocrine cells

produce hormones

survive

multiple signals

grow and divide

additional signals

differentiate

additional signals

die

no signals-cell suicide/apoptosis

endocrine signaling

hormones through blood/sap can act over long distances

paracrine signaling

induce a response in neighbor cell. May enter through bloodstream but have too low concentration to travel long distances

Autocrine

chemicals cause response in the same cell that made it

contact-dependent

requires physical interaction of cells; membrane bound signal molecule

receptor

required for cell to respond, usually activated by one type of signal

extracellular signals are 

large and hydrophilic and need receptors

cell surface receptors can take

• small uncharged polar molecules

• large uncharged molecules

• ions

intracellular receptors can take

small nonpolar molecules

small nonpolar molecules

O2, CO2, N2, steroid hormones

Small uncharged polar molecules

H2O, ethanol, glycerol

Large uncharged polar molecules

glucose, nucleosides, some amino acids

ions

H+, Na+, K+, Ca2-, Cl-, Mg2+, HCO3-

intracellular pathway of action

primary response

• lipid soluble hormone diffuses through plasma membrane

• hormone binds with receptor in cytoplasm, makes receptor-hormone complex

• receptor-hormone complex enters nucleus and starts transcription

• transcribed mRNA translates into proteins

Extracellular pathway of action

receptor does not go into cell

• water-soluble hormones are membrane insoluble and must bind to receptors

• binding activates g protein

• g protein makes adenylyl cyclase

• adenylyl cyclase catalyzes conversion of cAMP from ATP, a secondary messenger

• cAMP activates protein kinase, which adds phosphate groups

• protein kinases phosphorylate proteins in cytoplasm

  • activates proteins so they can alter cell activity

the same signal can have different effects on target cells that have

• different receptors for the molecule

• different signal transduction pathways

• different proteins for carrying out the response

slow cell responses

• involve change in gene expression and synthesis of new proteins

  • cell differentiation

  • cell growth

  • cell division

fast cell responses

• do not need change in gene expression

  • cell movement

  • secretion

  • metabolism

primary transcriptional response

direct induction of transcription in a small number of genes within 30 minutes

secondary transcriptional response

products of primary response activate other genes

cell surface receptors

bind to extracellular signal molecules and convert the message into multiple intracellular signaling molecules to alter cell behavior

ion channel coupled receptors

change permeability of plasma membrane to specific ions to make an electric current

G protein coupled receptors

activate g proteins that activate an enzyme/ion channel in plasma membrane, initiating intracellular signaling cascade

enzyme coupled receptors

act as enzymes, when stimulated they activate a variety of intracellular signaling pathways

kinase

catalyzes addition of phosphate groups to molecules. attach phosphate groups to proteins

phosphotase

catalyzes hydrolytic removal of phosphate group from molecule

signaling by phosphorylation

• largest class

• affected by 

  • kinases: serine/threonine, and tyrosine

    • -OH group is always polar

  • phosphotases

signaling by GTP binding

activation state depends on whether GTP or GDP is bound

many have the ability to hydrolyze GPT to GDP

Trimeric GTP Binding proteins (G proteins)

relay messages from G-protein coupled receptors

Monomeric GTPases

• relay intracellular signal

• uses 2 sets of regulatory proteins two sets to bind and hydrolyze GTP

GTP

Guanine exchange factors

• promote exchange of GDP for GTP

• GTPase activating proteins

• promote GTP hydrolysis

GTP Protein coupled receptors

• largest family of cell surface receptors

  • more than 700 in humans

• all have a similar structure

  • single polypeptide chain that spans the membrane 7 times

signals can be

• proteins

• small peptides

• amino acid derivatives

• fatty acid derivatives

G proteins

• 20 different kinds of mammalian G proteins

  • activated by different target proteins

  • g protein interaction with ion channel causes sudden changes in stage and behavior cell

G-protein interactions with enzymes are

slow and complex

• produce additional signaling molecules

adenyl cyclase —>

Cyclic AMP

Phospholipase C —>

Inositol triphosphate

Enzyme linked cell surface receptors

cystoplasmic domains act as enzymes and make a complex with the enzyme

• receptors for many growth factors

epidermal growth factor

1982

Largest class of enzyme linked cell surface receptors

tyrosine kinases

• when stimulated, start phosphorylating

• ligand binding causes two receptors to dimerize which activates a large signal cascade to start enzyme activity

Ras is activated by

receptor tyrosine kinase

Monomeric GPTas causes

Phosphorylation cascade

which amino acids phosphorylate and activate in sequence

Serine/Threonine

MAP kinase pathwaty

Mitogen activated protein activates Ras

how many human cancers have Ras

30%