DESCRIPTION: This is a proposal to study signal transduction pathways, especially those involving protein kinases, stimulated by the multifunctional cytokines or neurokines, LIF and CNTF. The applicant's feasibility data upon which this proposal is based are: 1) the low affinity LIF receptor (LIFR) can be phosphorylated by MAPK in LIF- stimulated cell lysates; 2) the receptor gp130 polypeptide can also be phosphorylated on serine in LIF-stimulated cells; 3) the induction of choline acetyltransferase (ChAT) gene transcription by CNTF utilizes PKC dependent and independent pathways, while LIF uses only a PKC- independent pathway. The applicant proposes to pursue these observations by: 1) identifying the site of phosphorylation of LIFR by MAPK and determine the functional significance, if any, of the phosphorylation; 2) identify the kinase that phosphorylates gp130 on serine, determine the phosphorylation sites, and functional consequences of phosphorylation; 3) examine the differential requirements for PKC in CNTF- versus LIF-stimulated activities.
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