|
|
|
|
A more recent version of this article appeared on October 1, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on February 24, 2006
Revised on June 20, 2006
Accepted on July 17, 2006
||
Departments of *Molecular Genetics and
Chemical Research Support, The Weizmann Institute of Science, Rehovot 76100, Israel;
Department of Physiology and Pharmacology, Tel Aviv University Medical School, Tel Aviv 69978, Israel;
Department of Pharmacology, New York University Medical School, New York, NY 10016
Monitoring Editor: Carl-Henrik Heldin
Tyrosine phosphatases Epsilon (PTP
) and Alpha (PTP
) are closely related and share several molecular functions, such as regulation of Src family kinases and voltage-gated potassium (Kv) channels. Functional interrelationships between PTP
and PTP
and the mechanisms by which they regulate K+ channels and Src were analyzed in vivo in mice lacking either or both PTPs. Lack of either PTP increases Kv channel activity and phosphorylation in Schwann cells, indicating these PTPs inhibit Kv current amplitude in vivo. Open probability and unitary conductance of Kv channels are unchanged, suggesting an effect on channel number or organization. PTP
inhibits Kv channels more strongly than PTP
; this correlates with constitutive association of PTP
with Kv2.1, driven by membranal localization of PTP
. PTP
, but not PTP
, activates Src in sciatic nerve extracts, suggesting Src deregulation is not responsible exclusively for the observed phenotypes and highlighting an unexpected difference between both PTPs. Developmentally, sciatic nerve myelination is reduced transiently in mice lacking either PTP and more so in mice lacking both PTPs, suggesting both PTPs support myelination but are not fully redundant. We conclude that PTP
and PTP
differ significantly in their regulation of Kv channels and Src in the system examined, and that similarity between PTPs does not necessarily result in full functional redundancy in vivo.
, Denmark.
Address correspondence to:
Ari Elson (ari.elson{at}weizmann.ac.il)
This article has been cited by other articles:
![]() |
L. A. Samayawardhena and C. J. Pallen Protein-tyrosine Phosphatase {alpha} Regulates Stem Cell Factor-dependent c-Kit Activation and Migration of Mast Cells J. Biol. Chem., October 24, 2008; 283(43): 29175 - 29185. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Sines, S. Granot-Attas, S. Weisman-Welcher, and A. Elson Association of Tyrosine Phosphatase Epsilon with Microtubules Inhibits Phosphatase Activity and Is Regulated by the Epidermal Growth Factor Receptor Mol. Cell. Biol., October 15, 2007; 27(20): 7102 - 7112. [Abstract] [Full Text] [PDF] |
||||