TI  - Interaction of   <prot>IL-2R   beta</prot> and gamma c chains with  <prot>Jak1</prot>  and  <prot>Jak3</prot> :
      implications for XSCID and XCID.
PG  - 1042-5
AB  - <prot>Interleukin-2</prot> (<prot>IL-2</prot>) signaling requires the dimerization of the   <prot><prot>IL-2</prot>
      receptor beta</prot>.(<prot>IL-2R beta</prot>)   and   common gamma (gamma c)   chains. Mutations of
      gamma c can result in X-linked severe combined immunodeficiency (XSCID).
      <prot>IL-2</prot>, <prot>IL-4</prot>, <prot>IL-7</prot> (whose receptors are known to contain gamma c), and <prot>IL-9</prot>
      (whose receptor is shown here to contain gamma c) induced the tyrosine
      phosphorylation and activation of the Janus family tyrosine kinases <prot>Jak1</prot>
      and <prot>Jak3</prot>.  <prot>Jak1</prot>  and  <prot>Jak3</prot>  associated with  <prot>IL-2R beta</prot>  and  gamma c ,
      respectively; <prot>IL-2</prot> induced  <prot>Jak3</prot> - <prot>IL-2R beta</prot>  and increased  <prot>Jak3</prot> - gamma c 
      associations. Truncations of gamma c, and a gamma c, point mutation
      causing moderate X-linked combined immunodeficiency (XCID), decreased
       gamma c - <prot>Jak3</prot>  association. Thus, gamma c mutations in at least some XSCID
      and XCID patients prevent normal <prot>Jak3</prot> activation, suggesting that
      mutations of <prot>Jak3</prot> may result in an XSCID-like phenotype.
AD  - Laboratory of Molecular Immunology, National Heart, Lung, and Blood
