Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are many known growth factors/cytokines that induce skeletal muscle satellite cell proliferation. Currently, the signaling mechanisms in which these growth factors/cytokines activate satellite cell proliferation are not completely understood. Here, we sought to determine signaling mechanisms by which leukemia inhibitory factor (LIF) induces satellite cell proliferation in culture. First, we confirmed that LIF induces proliferation of C2C12 immortalized myoblasts and cultured primary rat satellite cells. In addition, we also found that this increase in proliferation can be inhibited by incubation of the cells in tyrphostin AG 490, a specific inhibitor of Janus-activated kinase (JAK) 2 activity. Furthermore, we also found that incubation of the cells at various time points with LIF (10 ng/ml) induces a significant, transient increase in JAK2 phosphorylation, signal transducers and activators of transcription (STAT3) phosphorylation, and STAT3 transcriptional activity. Increases in the STAT3-sensitive endogenous SOC3 protein followed these transient increases in STAT3 activation. In addition, AG 490 inhibited the increase in STAT3 phosphorylation. Finally, LIF did not change the phosphorylation status of extracellular signal-regulated protein kinase (ERK)1/2 or affect the phosphorylation status of Akt/protein kinase B. However, LY-294002, an inhibitor of phosphoinositide 3-kinase, blocked LIF-induced proliferation of satellite cells. These data suggest that LIF induces satellite cell proliferation by activation of the JAK2-STAT3 signaling pathway, suggesting that this may be an important pathway in muscle growth and/or hypertrophy.
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PMID:Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell proliferation. 1205 89

The cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is a sequence of communications between proteins in a cell, and it is associated with various processes such as cell division, apoptosis, mammary gland development, lactation, anti-inflammation, and immunity. The pathway is involved in transferring information from receptors on the cell surface to the cell nucleus, resulting in the regulation of genes through transcription. The Janus kinase 2 (JAK2), signal transducer and activator of transcription A and B (STAT5 A & B), STAT1, and cytokine signaling suppressor 3 (SOCS3) are the key members of the JAK-STAT pathway. Interestingly, prolactin (Prl) also uses the JAK-STAT pathway to regulate milk production traits in dairy cattle. The activation of JAK2 and STATs genes has a critical role in milk production and mastitis resistance. The upregulation of SOCS3 in bovine mammary epithelial cells inhibits the activation of JAK2 and STATs genes, which promotes mastitis development and reduces the lactational performance of dairy cattle. In the current review, we highlight the recent development in the knowledge of JAK-STAT, which will enhance our ability to devise therapeutic strategies for bovine mastitis control. Furthermore, the review also explores the role of the JAK-STAT pathway in the regulation of milk production in dairy cattle.
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PMID:Role of the JAK-STAT Pathway in Bovine Mastitis and Milk Production. 3320 60