| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Molecular Pharmacology, University of Groningen, Groningen, Netherlands
2 Departments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Canada
3 Department of Pharmacology, University of Nevada School of Medicine, Reno, United States
4 Section of Thoracic Surgery, University of Manitoba, Winnipeg, Canada
5 Department of Molecular Pharmacology, University of Groningen, Groningen, Netherlands
* To whom correspondence should be addressed. E-mail: r.gosens{at}rug.nl.
Caveolae are abundant plasma membrane invaginations in airway smooth muscle that may function as pre-organized signalosomes by sequestering and regulating proteins that control cell proliferation, including receptor tyrosine kinases (RTKs) and their signaling effectors. We previously demonstrated, however, that p42/p44 MAP kinase, a critical effector for cell proliferation, does not co-localize with RTKs in caveolae of quiescent airway myocytes. Therefore we investigated the subcellular sites of growth factor-induced MAP kinase activation. In quiescent myocytes, though epidermal growth factor receptor (EGFR) was almost exclusively found in caveolae, p42/p44 MAP kinase, Grb2 and Raf-1 were absent from these membrane domains. EGF induced concomitant phosphorylation of caveolin-1 and p42/p44 MAP kinase; however, EGF did not promote the localization of p42/p44 MAP kinase, Grb2 or Raf-1 to caveolae. Interestingly, stimulation of muscarinic M2 and M3 receptors that were enriched in caveolae-deficient membranes also induced p42/p44 MAP kinase phosphorylation, but this occurred in the absence of caveolin-1 phosphorylation. This suggests that the localization of receptors to caveolae and interaction with caveolin-1 is not directly required for p42/p44 MAP kinase phosphorylation. Furthermore, we found that EGF exposure induced rapid translocation of EGFR from caveolae to caveolae-free membranes. EGFR trafficking coincided temporally with EGFR and p42/p44 MAPK phosphorylation. Collectively, this indicates that though caveolae sequester some receptors associated with p42/p44 MAP kinase activation, the site of its activation is associated with caveolae-free membrane domains. This reveals that directed trafficking of plasma membrane EGFR is an essential element of signal transduction leading to p42/p44 MAP kinase activation.
This article has been cited by other articles:
|
|
 |
|
  R. O. Nunes, M. Schmidt, G. Dueck, H. Baarsma, A. J. Halayko, H. A. M. Kerstjens, H. Meurs, and R. Gosens GSK-3/{beta}-catenin signaling axis in airway smooth muscle: role in mitogenic signaling Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1110 - L1118. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Penn and J. L. Benovic Regulation of Heterotrimeric G Protein Signaling in Airway Smooth Muscle Proceedings of the ATS, January 1, 2008; 5(1): 47 - 57. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Halayko, T. Tran, and R. Gosens Phenotype and Functional Plasticity of Airway Smooth Muscle: Role of Caveolae and Caveolins Proceedings of the ATS, January 1, 2008; 5(1): 80 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson, I. Nordstrom, K. Sward, and P. Hellstrand Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall Am J Physiol Cell Physiol, January 1, 2008; 294(1): C271 - C279. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
