Question

Cell Biology Tutorial - JAK/STAT Signaling Pathway

Answer 1

(this is a tutorial, not a question, please save all comments and questions for the end)

Answer 2

Receptor tyrosine kinases (RTKS) and cytokine receptors activate tyrosine kinases, which phosphorylate tyrosine residues on peptides, which can then activate signaling pathways involved in proliferation, differentiation, and metabolism.

Cytokine receptors activate a the JAK/STAT pathway which involves a STAT transcription factor that: binds to the active receptor and is phosphorylated by the JAK kinase, moving to the nucleus and activating transcription.

Answer 3

\({\bf{types~of~cytokines}}\)

interleukins: proliferation/function of T-cells/B-cells
interferons: secreted to induce enzymes involved in viral resistance
growth hormones: secreted by the pituitary glands, stimulates proliferation of many types of cells
prolactin: differentiation of epithelial cells in the mammary gand into acinar cells that produce milk

Answer 4

cont:

granulocyte colony-stimulating factor: granulocyte differentiation (bone marrow)
thrombopoietin: megakaryocyte differentiation (platelets)
erythropoietin (Epo): erythropoietin differentiation (blood cells)

Answer 5

\({\bf{receptor~homodimerization}}\)

Many of the aforementioned receptors activate kinase receptors by forming a dimer of two identical receptor proteins. Each receptor activates the JAK kinase, JAK2, it is bound to.

\({\bf{receptor~heterodimerization}}\)

Some cytokines bind to two different cytokine receptors, usually belonging to the JAK family.

Both these systems involve weak noncovalent bonds + strong molecular complementarity giving a low Kd.

Each JAK kinase supplies the enzymatic activity. They have an N-terminal domain that binds to the receptor, a C-terminal domain, and a pseudokinase domain that regulates kinase activity.

Answer 6

\({\bf{phosphotyrosine~phosphatases}}\)
SHP1: negatively regulates cytokine receptors by binding to the receptor and inactivating JAK. SH2 domains in SHP1 binds to the catalytic site in the inactive form; in the active form, SHP1 catalytic site is brought near the activation loop, adding a phosphate and activating the JACK kinase.

Answer 7

\({\bf{SOCS-proteins}}\) have SOCS boxes that recruit components of E3 ubiquitin ligases. the SH2 domain of SOCS binds to phosphotyrosines on the activated receptor, polyubiqutinylating the kinase, turning off the pathway.