We compared the role of tyrosine kinases in α1A-adrenergic receptor (AR) and growth factor receptor stimulation of mitogen-activated protein kinase pathways in PC12 cells. Norepinephrine (NE) (noradrenaline), epidermal growth factor (EGF) and nerve growth factor (NGF) caused different patterns of tyrosine phosphorylation in PC12 cells stably expressing α1A-ARs. NE increased tyrosine phosphorylation of focal adhesion-related kinase Pyk2 and a 70 kDa protein, probably paxillin, whereas EGF strongly stimulated tyrosine phosphorylation of the EGF receptor and cytokine-activated kinase Jak2. The EGF receptor inhibitor AG1478 inhibited activation of extracellular signal-regulated kinases (ERKs) by EGF but not by NE. EGF and NGF strongly activated tyrosine phosphorylation of Shc and caused association of Src-homology collagen (Shc) with growth-factor-receptor-bound protein 2 (Grb2); however, neither NE nor UTP caused substantial activation of the Shc/Grb2 pathway. NE, UTP, EGF and NGF all increased tyrosine phosphorylation of Src, and this was inhibited by the Src inhibitor PP2. However, PP2 inhibited ERK activation in response to NE and UTP, but not in response to EGF or NGF. PP2 also completely blocked NE-induced PC12 cell differentiation, but had no measurable effect on NGF-induced differentiation. These studies show that activation of mitogen-activated protein kinase pathways by G-protein-coupled receptors and tyrosine kinase receptors proceed through distinct molecular pathways in PC12 cells, and support an obligatory role for Src activation in mitogenic responses to α1A-ARs in these cells.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
December 1999
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Research Article|
December 08 1999
Activation of tyrosine kinases by α1A-adrenergic and growth factor receptors in transfected PC12 cells Available to Purchase
Hongying ZHONG;
Hongying ZHONG
1Department of Pharmacology, Emory University Medical School, Atlanta, GA 30322, U.S.A.
Search for other works by this author on:
Kenneth P. MINNEMAN
Kenneth P. MINNEMAN
1
1To whom correspondence should be addressed (e-mail kminneman@;pharm.emory.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
May 21 1999
Revision Received:
August 24 1999
Accepted:
October 13 1999
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 344 (3): 889–894.
Article history
Received:
May 21 1999
Revision Received:
August 24 1999
Accepted:
October 13 1999
Citation
Hongying ZHONG, Kenneth P. MINNEMAN; Activation of tyrosine kinases by α1A-adrenergic and growth factor receptors in transfected PC12 cells. Biochem J 15 December 1999; 344 (3): 889–894. doi: https://doi.org/10.1042/bj3440889
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |