Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myosin light chain kinase which phosphorylates g2 light chain of skeletal muscle myosin requires an activator for the activity (Yazawa, M., and Yagi, K (1977) J. Biochem. (Tokyo) 82, 287-289). This activator has now been identified as the modulator protein known to be a Ca2+-dependent regulator for phosphodiesterase, adenylate cyclase, and ATPases. The identification is based on the quantitative cross-reactivity of muscle activator protein and brain modulator protein in activating myosin light chain kinase and brain phosphodiesterase and identical properties of both proteins in regard to sensitivities to Ca2+, UV absorption spectra, UV absorption difference spectra with or without Ca2+, and mobilities upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of modulator protein, the activity of myosin light chain kinase was reversibly controlled by the physiological concentration of Ca2+. We suggest that two Ca2+-receptive proteins, i.e. modulator protein and troponin-C, may play roles in the contraction-relaxation cycle of skeletal muscle.
 ...
PMID:Identification of an activator protein for myosin light chain kinase as the Ca2+-dependent modulator protein. 62 40

Myosin light chain kinase (MLCK) and the kinase-related protein (KRP), also known as telokin, are the major independent protein products of the smooth muscle/non-muscle MLCK genetic locus. They share a common C-terminal part and major sites phosphorylated in vivo. Whereas MLCK is critically involved in myosin activation and contraction initiation in smooth muscle, KRP is thought to antagonize MLCK and to exert relaxation activity. Phosphorylation controls the MLCK and KRP activities. We generated two phosphorylation and site-specific antibodies to individually monitor levels of MLCK and KRP phosphorylation on critical sites. We quantified the level of KRP phosphorylation in smooth muscle before and after an increase in intracellular free Ca2+ and stimulation of adenylate cyclase, protein kinase C, and mitogen-activated protein kinases (MAP-kinases). Forskolin and phorbol-12,13-dibutyrate increased KRP phosphorylation at Ser13 from 25 to 100% but did not produce contraction in rat ileum. The level of Ser13 phosphorylation was not altered during Ca2+-dependent contraction evoked by KCl depolarization or carbachol, but subsequently increased to maximum during forskolin-induced relaxation. These data suggest that several intracellular signaling pathways control phosphorylation of KRP on Ser13 in smooth muscle and thus may contribute to relaxation. In contrast, phosphorylation level of Ser19 of KRP increased only slightly (from 30 to 40-45%) and only in response to MAP-kinase activation, arguing against its regulatory function in smooth muscle.
 ...
PMID:Novel phosphospecific antibodies for monitoring phosphorylation of proteins encoded by the myosin light chain kinase genetic locus. 1531 Feb 80