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PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells.
J Cell Sci. 2004 Dec 01; 117(Pt 25):6085-94.JC

Abstract

Recent studies suggest that the tyrosine kinase Src plays an important role in the hormonal regulation of extracellular signal-regulated kinases (ERKs) via cyclic AMP (cAMP). Src has also been proposed to mediate signals downstream of nerve growth factor (NGF). Here, we report that the cAMP-dependent protein kinase A (PKA) induced the phosphorylation of Src at residue serine17 (S17) in multiple cell types including PC12, Hek293, AtT-20 and CHO cells. In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF. In these cells, Rap1 is required for cAMP/PKA signaling to ERKs and also for the sustained activation of ERKs by NGF. The activation of Rap1 by both cAMP and NGF was blocked by PP2, an inhibitor of Src family kinases, and by a Src mutant incapable of being phosphorylated by PKA (SrcS17A), consistent with the requirement of PKA phosphorylation of Src at S17 in these actions. PP2 and SrcS17A also inhibited the Rap1-dependent activation of ERKs by both agents. These results strongly indicate that PKA phosphorylation of Src at S17 is essential for cAMP and NGF signaling in PC12 cells and identify PKA as an important downstream target of NGF. PKA phosphorylation of Src may therefore be required for Rap1 activation in PC12 cells.

Authors+Show Affiliations

The Vollum Institute, L474, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15546918

Citation

Obara, Yutaro, et al. "PKA Phosphorylation of Src Mediates Rap1 Activation in NGF and cAMP Signaling in PC12 Cells." Journal of Cell Science, vol. 117, no. Pt 25, 2004, pp. 6085-94.
Obara Y, Labudda K, Dillon TJ, et al. PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells. J Cell Sci. 2004;117(Pt 25):6085-94.
Obara, Y., Labudda, K., Dillon, T. J., & Stork, P. J. (2004). PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells. Journal of Cell Science, 117(Pt 25), 6085-94.
Obara Y, et al. PKA Phosphorylation of Src Mediates Rap1 Activation in NGF and cAMP Signaling in PC12 Cells. J Cell Sci. 2004 Dec 1;117(Pt 25):6085-94. PubMed PMID: 15546918.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PKA phosphorylation of Src mediates Rap1 activation in NGF and cAMP signaling in PC12 cells. AU - Obara,Yutaro, AU - Labudda,Kirstin, AU - Dillon,Tara J, AU - Stork,Philip J S, Y1 - 2004/11/16/ PY - 2004/11/18/pubmed PY - 2005/7/28/medline PY - 2004/11/18/entrez SP - 6085 EP - 94 JF - Journal of cell science JO - J Cell Sci VL - 117 IS - Pt 25 N2 - Recent studies suggest that the tyrosine kinase Src plays an important role in the hormonal regulation of extracellular signal-regulated kinases (ERKs) via cyclic AMP (cAMP). Src has also been proposed to mediate signals downstream of nerve growth factor (NGF). Here, we report that the cAMP-dependent protein kinase A (PKA) induced the phosphorylation of Src at residue serine17 (S17) in multiple cell types including PC12, Hek293, AtT-20 and CHO cells. In PC12 cells, Src phosphorylation on S17 participates in the activation of the small G protein Rap1 by both cAMP and NGF. In these cells, Rap1 is required for cAMP/PKA signaling to ERKs and also for the sustained activation of ERKs by NGF. The activation of Rap1 by both cAMP and NGF was blocked by PP2, an inhibitor of Src family kinases, and by a Src mutant incapable of being phosphorylated by PKA (SrcS17A), consistent with the requirement of PKA phosphorylation of Src at S17 in these actions. PP2 and SrcS17A also inhibited the Rap1-dependent activation of ERKs by both agents. These results strongly indicate that PKA phosphorylation of Src at S17 is essential for cAMP and NGF signaling in PC12 cells and identify PKA as an important downstream target of NGF. PKA phosphorylation of Src may therefore be required for Rap1 activation in PC12 cells. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/15546918/PKA_phosphorylation_of_Src_mediates_Rap1_activation_in_NGF_and_cAMP_signaling_in_PC12_cells_ L2 - https://journals.biologists.com/jcs/article-lookup/doi/10.1242/jcs.01527 DB - PRIME DP - Unbound Medicine ER -