<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Niogret, Charlène</dc:creator>
  <dc:creator>Birchmeier, Walter</dc:creator>
  <dc:creator>Guarda, Greta</dc:creator>
  <dc:date>2019-10-25</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Somewhat counterintuitively, the tyrosine phosphatase SHP-2 (SH2 domain- containing protein tyrosine  phosphatase-2) is crucial for the activation of extracellular signal-regulated kinase  (ERK) downstream of  various growth factor receptors, thereby exerting essential developmental functions.  This phosphatase also  deploys proto-oncogenic functions and specific inhibitors have recently been  developed. With respect to the  immune system, the role of SHP-2 in the signaling of cytokines relevant for  myelopoiesis and myeloid  malignancies has been intensively studied. The function of this phosphatase  downstream of cytokines  important for lymphocytes is less understood, though multiple lines of evidence  suggest its importance. In  addition, SHP-2 has been proposed to mediate the suppressive effects of inhibitory  receptors (IRs) that  sustain a dysfunctional state in anticancer T cells. Molecules involved in IR signaling  are of potential  pharmaceutical interest as blockade of these inhibitory circuits leads to remarkable  clinical benefit. Here, we  discuss the dichotomy in the functions ascribed to SHP-2 downstream of cytokine  receptors and IRs, with a  focus on T and NK lymphocytes. Further, we highlight the importance of broadening  our understanding of  SHP-2′s relevance in lymphocytes, an essential step to inform on side effects and  unanticipated benefits of  its therapeutic blockade.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://susi.usi.ch/global/documents/319152</dc:identifier>
  <dc:identifier>https://n2t.net/ark:/12658/srd1319152</dc:identifier>
  <dc:identifier>https://susi.usi.ch/documents/319152/files/Niogret_FrontiersMedia.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.02468</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/ark/12658/srd1319152</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>CC BY</dc:rights>
  <dc:source>Frontiers in immunology. - 2019, vol. 10, no. 2468, p. 1-11</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">SHP-2 phosphatase</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">SHP-2 inhibitors</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">PTPN11 gene</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">Lymphocytes</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">Cytokine</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">Inhibitory receptors of lymphocytes</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">PD-1</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Cancer</dc:subject>
  <dc:subject>info:eu-repo/classification/udc/57/59</dc:subject>
  <dc:title xmlns:ns9="xml" ns9:lang="en">SHP-2 in lymphocytes’ cytokine and inhibitory receptor signaling</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>