JAK-STAT pathway and myogenic differentiation

Abstract

Myogenic differentiation plays an important role in muscle regeneration and is regulated by two transcription factor families, MRFs and MEF2, which induce differentiation of myoblasts through expression of the muscle-specific gene, myogenin. In addition, many intracellular signaling pathways are also involved in myogenic differentiation, including p38 MAPK, ERK/MAPK and PI3K/AKT. The JAK-STAT pathway is activated by various cytokines and positively or negatively regulates the differentiation of myoblasts. JAK1 plays a notable role in proliferation; whereas, JAK2 and JAK3 function mainly in differentiation. The STATs, molecules downstream of JAK, regulate myogenesis. With JAK1, STAT1 promotes proliferation, while STAT3 has a dual effect on proliferation and differentiation. The JAK-STAT negative regulator, SOCS, is also associated with myogenesis; although, its role is controversial. In this review, we will discuss the role of the JAK-STAT pathway on myogenic differentiation.

Regulation of the Na⁺,Cl^- Coupled Creatine Transporter CreaT (SLC6A8) by the Janus Kinase JAK3

“…Instead, JAK3 may be effective by regulating other signalling molecules or transporters which indirectly compromise the function of CreaT. JAK3 sensitive signalling includes Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway [64]. In theory, JAK3 could, through this pathway, up-regulate the expression of CreaT regulating signalling molecules.…”

Effects of Double Transgenesis of Somatotrophic Axis (GH/GHR) on Skeletal Muscle Growth of Zebrafish (Danio rerio)

“…26 PI3K/Akt and MEK/ERK pathways can activate genes that code not only for myogenic regulatory factors but also for muscle proteins. 27,28 In this study, expression of myod and myf5 was, respectively, 73% and 58% lower in the double transgenics when compared to the GH group. Regarding muscle proteins, the gene that codifies for the MYHC4 presented the largest decrease (97%) when comparing the GH to the GH/GHR group.…”

Case report Extracardiac rhabdomyomas – presentation of two cases with analysis of AKT/mTOR and ERK1/2 signaling

“…The exact mechanism of this activation remains unestablished, if its background is genetic, epigenetic, or posttranslational. Probably coactivation of these pathways promotes tumorigenesis, being in parallel, involved in a myogenic differentiation [15]. Keeping in mind, that especially adult RM have relatively high propensity for recurrence, our findings suggest a potential way for their target therapy in the unresectable cases.…”

“…AKT has connections with many transduction pathways and regulates apoptotic pathway and cellular proliferation. AKT-independent mechanisms of mTOR activation also exist, while both kinases are linked via positive and negative feedback loops [14][15]. In comparison to the extracardiac RM, in cardiac tumors, p-AKT upregulation was not detected, while mTOR and Erk, and their substrates were hyperactive [2,3].…”