Reflecting on the New Year with Janus and Jak


Posted by Ken B on Jan 3, 2018 3:00:00 AM

With the arrival of the New Year, we all look back on 2017 and anticipate the coming year. CST scientists have been working hard to develop new antibodies and reagents to enable your next successful experiment in 2018!

In Roman mythology, the New Year and the month of January are associated with Janus, the god of transitions and doorways (1). Janus is best known for having two faces: one looking to the past, and one to the future. Janus also lends his name to the Janus kinase (Jak) family of nonreceptor tyrosine kinases.

Jak1 and Jak2 were identified by Wilks and colleagues in the early ‘90’s using a degenerate PCR strategy to search for novel kinases related to Tyk2 (2). In describing the Jak proteins, the authors noted that they each contain two kinase domains (although it turned out that one is non-catalytic), so naming them after the two-faced Janus was natural. You might be able to see a resemblance between the 3D protein model of Jak1 (3-4) and an ancient Roman sculpture of Janus:

2018_01_12_IMM_276_JAKSTAT_Blog_image.png

Sculpture of Janus (left) superimposed with a bivalent antibody, and structural model of Jak1 kinase and pseudokinase domains (right.)

Jak/Stat Signaling

Jak1 and Jak2 serve as scaffolders in transducing signaling from cytokines and interferons. Upon ligand-receptor activation, Jak1/2 is recruited to the receptor where they phosphorylate it and themselves, leading to docking and activation of Stat and other SH2-containing adaptors, and subsequent changes in gene transcription. Stark and Darnell provide an interesting retrospective of the efforts by multiple labs to map the Jak/Stat pathway (5). While initially described in the context of interferon, it is now known that Jak/Stat is involved in mediating signaling responses to a number of cytokines and growth factors, and is important in hematopoiesis, immune responses, development, and cancer (6-8).

From all of us at CST, here's to new scientific breakthroughs in the New Year!

Explore the interactive Jak/Stat signaling pathway here.

References:
  1. Wasson DL (2015), “Janus”, Ancient History Encyclopedia.
  2. Wilks AF et al (1991) Mol Cell Biol 11(4): 2057-65.
  3. Zhang D et al. (2016) J Mol Biol 428:4651-4668. 
  4. Biasini M., et al. (2014). Nucleic Acids Res. 42 (W1): W252-8.
  5. Stark GR and Darnell JE (2012) Immunity 36(4): 503-14.
  6. Yu H et al. (2009) Nat Rev Cancer 9(11), 798–809.
  7. Vainchenker W, Constantinescu SN (2013) Oncogene 32, 2601–13.
  8. O'Shea JJ et al. (2015) Annu Rev Med 66:311-28.