Skeletal muscle satellite cell-derived myoblasts are mainly responsible for postnatal muscle growth and injury-induced regeneration. However, the cellular signaling pathways that control proliferation and differentiation of myoblasts remain poorly defined. Recently, we found that JAK1/STAT1/STAT3 not only participate in myoblast proliferation but also actively prevent them from premature differentiation. Unexpectedly, we found that a related pathway consisting of JAK2, STAT2, and STAT3 is required for early myogenic differentiation. Interference of this pathway by either a small molecule inhibitor or small interfering RNA inhibits myogenic differentiation. Consistently, all three molecules are activated upon differentiation. The pro-differentiation effect of JAK2/STAT2/STAT3 is partially mediated by MyoD and MEF2. Interestingly, the expression of the IGF2 gene and the HGF gene is also regulated by JAK2/STAT2/STAT3, suggesting that this pathway could also promote differentiation by regulating signaling molecules known to be involved in myogenic differentiation. In summary, our current study reveals a novel role for the JAK2/STAT2/ STAT3 pathway in myogenic differentiation.

Protein kinase C (PKC) play critical roles in many cellular functions including differentiation, proliferation, growth, and survival. However, the molecular bases governing PKC's substrate recognitions remain poorly understood. Here we determined the structure of PKCι in complex with a peptide from Par-3 at 2.4 Å. PKCι in the complex adopts catalytically competent, closed conformation without phosphorylation of Thr402 in the activation loop. The Par-3 peptide binds to an elongated groove formed by the N- and C-lobes of the kinase domain. The PKCι/Par-3 complex structure, together with extensive biochemical studies, reveals a set of substrate recognition sites common to all PKC isozymes as well as a hydrophobic pocket unique to aPKC. A consensus aPKC's substrate recognition sequence pattern can be readily identified based on the complex structure. Finally, we demonstrate that the pseudosubstrate sequence of PKCι resembles its substrate sequence, directly binds to and inhibits the activity of the kinase.

A relay photocatalytic cascade reaction for the synthesis of 3-amino-1-(difluoromethylidene)tetralins was described. The reaction used readily available N-Boc protected arylalanines and bulk industrial chemical 2-bromo-3,3,3-trifluoropropene (BTP) as the starting materials combining two photoredox catalytic cycles with a single photocatalyst. In the first catalytic cycle, the defluorinative coupling of N-Boc arylalanines with BTP provided 2-bromo-1,1-difluoroalkenes. In the second catalytic cycle, 2-bromo-1,1-difluoroalkenes underwent intramolecular radical cyclization by photoredox activation of C(sp 2 )À Br bond, affording the desired 3-amino-tetralins bearing an exo-difluoroethylene unit in good yields. Moreover, the reactions of 3-aryl propanoic acids and BTP for the construction of 1-(difluoromethylidene)tetralins were also demonstrated.