A Role of Membranes in the Activation of a New Multifunctional Protein Kinase System

Abstract

A new multifunctional protein kinase, which normally exists as an inactive form in the soluble fraction in mammalian tissues, attaches to membranes to exhibit full enzymatic activity. A low concentration of Ca2+ is absolutely necessary for this activation. This process is reversible. cAMP shows no effect. The active factors in membranes are phosphatidylinositol, phosphatidylserine, phosphatidic acid, diphosphatidylglycerol, and phosphatidylethanolamine in that order. Phosphatidylcholine and sphingomyelin are far less effective. Cytoplasmic as well as other membrane fractions from various tissues are active in supporting the enzymatic activity. A possible role of this Ca2+ and phospholipid-activated protein kinase system in transmembrane control is proposed.

A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum

“…To determine whether TPA functions through the activation of protein kinase C, the ileal strip was superfused with medium containing a nonpromoter analog of TPA, 4cu-PDD [25]. This agent showed no significant effect either alone or in combination with A23 187.…”

Phosphorylation of ribosomal protein S6 and a peptide analogue of S6 by a protease‐activated kinase isolated from rat liver

“…The presence of an enzyme resembling rabbit reticulocyte protease-activated kinase I [ 15,221 could explain the appreciable phosphorylation of the 23-kDa (SlO) ribosomal pro&n [19]. Another possible enzyme is the Ca*+-phospholipiddependent protein kinase that can be activated proteolytically [30], can phosphorylate S6 [ 171 and appears to be present in liver cells [3 11. However, this enzyme may have been eliminated by the CMSepharose step because of its low affinity for cation-exchange resins [32].…”

Calcium‐activated, phospholipid‐dependent protein kinase in rat pancreas islets of langerhans

“…Synthetic diolein was purchased from Nakarai Chemicals. [7.32p] ATP, calf thymus H1 histone, various lipids, and other chemicals employed for the present studies were prepared as specified in [10][11][12][13][14][15][16]. All reagents were taken up in water which was prepared by a double distillation apparatus followed by passing through a Chelex 100 column to remove Ca 2÷ as in [13].…”

“…This PI turnover has been proposed to be intimately related to glucose-induced insulin release [7][8][9], but the definitive mechanism involved has not yet been clarified. In [ 10,11 ], a new species of protein kinase (protein kinase C) was described which absolutely requires Ca 2+ and phospholipid. Protein kinase C is usually present as an inactive form, but is activated by diacylglycerol which may be transiently produced from PI during its receptor-linked turnover [12,13].…”