Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway transmits information received from extracellular polypeptide signals, through transmembrane receptors, directly to target gene promoters in the nucleus, providing a mechanism for transcriptional regulation without second messengers. Evolutionarily conserved in eukaryotic organisms from slime molds to humans, JAK-STAT signaling appears to be an early adaptation to facilitate intercellular communication that has co-evolved with myriad cellular signaling events.

Key elements of the JAK-STAT pathway. Peter Znamenkiy, Wikipedia, public domain.

Mnemonic

J
JAK3 defect causes a form of SCID.
Janus
"Just fine" B cells (T-/B+/NK-)

Type I cytokine receptors are mediated through JAK/STAT and bind: IL-2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, GM-CSF.

IL7R plays a critical role in the V(D)J recombination during lymphocyte development. A defect in IL-7RA leads to SCID (T-/B+/NK+).

CD markers for central vs. effector memory T cells:

Central memory T cells: CD45RA-, CD27+, CCR7+, CD62L+

Effector memory T cells: CD45RA-, CD27-, CCR7-, CD62L-

A 3-month-old boy us diagnosed with JAK 3 SCID with symptoms of pneumonia, diarrhea and failure to thrive. Which CD markers will be in relatively normal numbers on flow cytometry?

(A) CD8

(B) CD20

(C) CD19

(D) CD56

(E) CD45RA

(F) CD4

Answer: B, C - markers of B cells.

JAK3 deficiency affects T-cells (CD4, CD8, CD45RA) and NK cells (C D56) and causes SCID T-B+/NK-.

Severe combined immunodeficiency (SCID) - 4 groups according to T/B/NK cells (click to enlarge the image).

A JAK inhibitor is the first approved drug (Jakafi) to treat myelofibrosis (NYTimes, 2011).

References

A Road Map for Those Who Don't Know JAK-STAT. Science 31 May 2002: Vol. 296. no. 5573, pp. 1653 - 1655, DOI: 10.1126/science.1071545.

Published: 05/09/2010
Updated: 11/15/2011