JAK/STAT pathway
(I also put in this outline a paper suggesting a useful organizational scheme)

J. E. Darnell, Jr., STATs and gene regulation, Science 277, 1997, 1630-1635

there is a page in Alberts et al (p. 767) on tyrosine-kinase-associated receptors & non-receptor tyrosine kinases

JAK = Janus kinase (or, fondly, "just another kinase")
Cytokine (small proteins which mediate proliferation or differentiation); receptor ligands:
interferon alpha beta and gamma, interleukins 2-7, 10-13 & 15, erythropoietin, growth hormone, prolactin, thrombopoietin

STAT = signal transducers and activators of transcription
gets phosphorylated on tyrosine and then dimerizes by phosphotyrosines (pY) on SH2's
SH = src homology
TRANSPARENCY (Fig.1, Darnell,1997)-have domains (SH2 & 3, TAD=transactivation domain)
protein is 750 - 850 amino acids in length
7 mammalian STAT genes -> at least 12 proteins from multiple mRNA splicing
specific ligands activate specific STATs in specific cell types
knockouts have shown that 5 of the 7 known STATs have specific roles in adult cells
TRANSPARENCY Table 1
STATs bind specific nucleotide sequences
marelle (an embryonic lethal) is Drosophila null mutant, and Dictyostelium has STAT => ancient

JAK STAT pathway TRANSPARENCY (Fig. 2, Darnell, 1997)

A. H. Brivanlou and J.E.Darnell Jr., Signal transduction and the control of gene transcription, Science 295, 813-818, 2002

There are about 200-300 general transcription factors, coactivators, etc. that combine with RNA polymerase in mammals.
There are more (2000-3000 that bind specific DNA sequences and activate transcription.
TRANSPARENCY (Fig. 1) organization
Constitutive (in all cells, like CCAAT binding protein) vs regulatory
Regulatory: "Developmental (go into nucleus directly like Hox cluster of homeobox genes sequentially expressed anterior to posterior) vs signal dependent.(1, 2, 3)
1. steroid receptor, about 50, all but glucocorticoid start in nucleus
2. activation by internal (cell autonomous signals) (new and presently esoteric)
3. cell surface receptors (a- resident nuclear factors, b- latent cytoplasmic factors)
a. RTK and G protein-coupled receptors lead to serine phorphorylation cascade
b. TRANSPARENCY (Fig 2) Many in animals, none in fungi or plants (phosphorylation, proteolysis)
TRANSPARENCY (Fig. 3) receptor activation delivers active transcription factor to the nucleus.
SMAD (like for TGFbeta), STAT (above, this outline), Hh (a recent outline)
TRANSPARENCY (Fig. 3 continued)

References

A. H. Brivanlou and J.E.Darnell Jr., Signal transduction and the control of gene transcription, Science 295, 813-818, 2002This page was last updated on March 21, 2002

J. E. Darnell, Jr., STATs and gene regulation, Science 277, 1997, 1630-1635

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