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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS034010-04
Application #
2669055
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Oliver, Eugene J
Project Start
1995-05-01
Project End
1999-02-28
Budget Start
1998-03-01
Budget End
1999-02-28
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Nathanson, Neil M (2012) Regulation of neurokine receptor signaling and trafficking. Neurochem Int 61:874-8
Port, Martha D; Laszlo, George S; Nathanson, Neil M (2008) Transregulation of leukemia inhibitory [corrected] factor receptor expression and function by growth factors in neuroblastoma cells. J Neurochem 106:1941-51