Mitogen-activated protein kinase and proliferation of human
vascular smooth muscle cells.
Mii, Shinsuke, Raouf A Khalil, Kathleen G Morgan, J. Anthony Ware, K
Craig Kent.
Departments of Surgery (Division of Vascular Surgery) and Medicine,
Beth Israel Hospital, and Program in Smooth Muscle Research, Harvard
Medical School, Boston, MA 02215
APStracts 2:0286H, 1995.
The intracellular messenger mitogen-activated protein kinase (MAP-K)
is activated in vascular smooth muscle cells (SMC) by various growth
factors as well as by agonists that have no proliferative effect. We
explored the hypotheses SMC proliferation is associated with a
specific pattern of MAP-K activation, by evaluating the kinetics of
MAP-K activation and tyrosine phosphorylation and the intracellular
location of MAP-K in SMC following addition of agonists of varying
mitogenic potential. A peak in MAP-K activation and tyrosine
phosphorylation occurred three to ten minutes after the addition of
agonists to SMC derived from human saphenous vein (early phase),
followed by a plateau of activity which was variable in duration
(late phase). A correlation was not found between mitogenicity and
the degree to which MAP-K became activated or tyrosine phosphorylated
in the early phase. However, the duration of MAP-K activation and
tyrosine phosphorylation correlated strongly with the ability of
agonists to stimulate SMC proliferation. Nuclear translocation of
MAP-K was associated with SMC proliferation, although the degree to
which each agonist induced nuclear translocation did not parallel its
mitogenic potential. The relative dependency of all three events on
protein kinase C (PKC) differed for each agonist and was greater in
the late versus the early phase. Thus, in human SMC, nuclear
translocation of MAP-K and prolonged activation and tyrosine
phosphorylation of MAP-K are associated with growth factor induced
mitogenesis.
Received 15 March 1995; accepted in final form 21 June 1995.
APS Manuscript Number H249-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.