Mitogen-Activated Protein Kinase Activation in Contractile versus Proliferative Smooth Muscle

COMPARISON OF MITOGEN-ACTIVATED PROTEIN KINASE ACTIVATION IN CONTRACTILE VERSUS PROLIFERATIVE SMOOTH MUSCLE  

MAP-kinases are implicated in several cell cycle transition checkpoints, including GO/Gl, Gl/S, and G2/M (Gotoh et al, 1991 Tamemoto et al, 1992 Watson etal, 1993). In the specific case of cultured vascular smooth muscle, Watson et al. (1993) have shown that MAPK is important for GO/Gl transitions. MAPK activity in quiescent cells peaks within minutes of serum stimulation and then declines to near basal levels during progression through the cell cycle. Clearly, MAPK plays a very important role in proliferative smooth muscle physiology. 

Other work has shown that MAPK is subject to regulation by intracellular cAMP. Agents that increase intracellular cAMP inhibit MAPK in fibroblasts, adipocytes, and CHO cells (Hordijkef a/., 1994 Sevetson et al., 1993 Wu et al., 1993). In human aortic smooth 

FIGURE 4 Schematic depicting the potential roles for MAPK in contractile versus proliferative (or cultured) smooth muscle. MAPK is activated in response to stimulation by growth factors, stretch, and pharmacological agents. This process can be inhibited by cAMP and cAMP-dependent protein kinase. Once activated, MAPK phos-phorylates a number of intracellular proteins (both cytoplasmic and nuclear) that result in an alteration of growth and proliferation in cultured cells. In contractile smooth muscle, MAPK phosphorylation of caldesmon may lead to alterations in muscle contractility or actin filament structure. 

There are two isoforms of MAPK in contractile, vascular, smooth muscle—p42MAPK p44MAPK—anj 

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