In both expression systems, we obtained specific actin phosphorylation and located the catalytic domain in the N-terminal half. To prove the intrinsic phosphorylation activity of AFK, full-length or partial cDNA fragments were expressed both in a reticulocyte lysate and in Escherichia coli. Whereas the N-terminal domain does not show any significant similarity to protein sequences from databases, there are six complete kelch repeats in the protein that comprise almost the entire C-terminal half of the molecule. The cDNA deduced amino acid sequence reveals two major domains of approximately 35 kDa each that are separated by a hinge-like proline/serine-rich segment of 50 residues. The quotes contained in this interview synopsis were edited for clarity.Actin-fragmin kinase (AFK) from Physarum polycephalum specifically phosphorylates actin in the EGTA-resistant 1:1 actin-fragmin complex. It's sort of complex and multifactorial.”įor more information on scleroderma, view the full HCPLive interview segment above. “The systemic form is still really thought to be genetic susceptibility, but trying to disentangle all the really heterogeneous environmental exposures becomes very complicated because, like most autoimmune diseases, including lupus, or dermatomyositis, there's usually not a single trigger. “And that's been validated in a number of studies,” she stated. And we know there are autoantibody associations that really are intrinsic to rendering that diagnosis, and even the skin-limited form called morphea.”Īrkin also added that trauma is actually a common trigger for where these patches develop in the morphea subtype of the condition. “Who then, in the appropriate environmental exposure, develop 1 of these 2 subtypes. “The truth is, we still don't fully understand the root cause for either one, and like many auto inflammatory diseases, the working hypothesis is that there are patients who are genetically susceptible,” Arkin explained. She added that when looking at the epidemiology, and for kids in particular, morphea is certainly more common than the systemic forms of scleroderma. “We think about autoantibody profiles helping to inform the subtype, whereas morphea, which is more skin-limited, really is a clinical diagnosis and there's not a lot of utility in checking autoantibody associations, because, again, the kind of monitoring and surveillance really is different,” Arkin said. She added that there are really different consensus criteria around each, particularly for the more systemic forms. So the first question is what subtype are we dealing with, because there is ‘systemic scleroderma’, which is more of a systemic autoimmune disease that can have multi-organ manifestations…and then there's localized scleroderma which is which is otherwise known as morphea.”Īmong her key points, Arkin pointed out that both treatment and monitoring are quite different for the subtypes, so a correct diagnosis is vital. “And it has a whole different series of subtypes. “So scleroderma is sort of a big umbrella term that means hardened skin,” she explained. In this HCPLive interview, Lisa Arkin, MD, spoke about her experiences in the dermatology field treating patients with scleroderma, sharing her insights on the skin condition and its future.Īrkin is known for her work as a pediatric dermatologist and member of the Society for Pediatric Dermatology, University of Wisconsin School of Medicine & Public Health / American Family Children's Hospital.
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