Calcitonin gene-related peptide induces AP-1 activity by a PKA and c-fos-dependent mechanism in pre-B cells.
Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide with regulatory influences on immune and inflammatory responses and early B lymphocyte differentiation. Little is known about its cellular mechanisms. These studies examined whether CGRP induces c-fos. CGRP induced a transient concentration-dependent increase in c-fos in a CGRP receptor expressing pre-B cell line, 70Z/3. CGRP did not induce c-jun, jun B or jun D. A protein kinase A (PKA) inhibitor blocked c-fos induction by CGRP, suggesting that the mechanism depends on cAMP induction of PKA. CGRP induced AP-1 binding activity in the nucleus, indicating that CGRP regulates expression of specific target genes. CGRP also induced c-fos in B220(+) enriched cells from bone marrow. These results suggest that regulatory influences of CGRP on early B cells and in other tissues can involve a cAMP/PKA, c-fos/AP-1-dependent pathway for regulation of specific genes.
McGillis
Joseph P
JP
Department of Microbiology and Immunology, University of Kentucky College of Medicine, Lexington, KY 40536, USA. jpmcgi01@uky.edu
Miller
Christopher N
CN
Schneider
David B
DB
Fernandez
Stefan
S
Knopf
Melissa
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D017868:Cyclic AMP-Dependent Protein Kinases; D015740:Calcitonin Gene-Related Peptide