Physiological Roles Of The Ca2+/Cam-Dependent Protein kinase Cascade In Health and Disease

Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

“…Calmodulin (CaM), a major calcium-dependent protein, plays an important role in infl ammation and metabolism. CaM activates a number of protein kinases, such as CaMKI, II, and IV ( 21,22 ). Relevant to this study, CaMKII has been shown to inhibit adipocyte differentiation in response to infl ammatory PGs such as PGF 2 ␣ ( 23 ).…”

A Regulatory Feedback Loop Between Ca2+/Calmodulin-dependent Protein Kinase Kinase 2 (CaMKK2) and the Androgen Receptor in Prostate Cancer Progression

“…Work from multiple laboratories including our own, has delineated a signaling pathway termed the Ca 2ϩ /calmodulin (CaM)-dependent kinase cascade (1). At its top level, the CaM kinase cascade consists of Ca 2ϩ /CaM-dependent kinase kinases (CaMKKs) 1(␣) and 2(␤) (2)(3)(4)(5).…”

“…The latter two are so named because they are also activated by distinct upstream kinase kinases, PDK1 and LKB1, respectively (6 -11). Upon activation, the downstream kinases regulate a remarkably broad spectrum of physiological processes including: gene transcription, mRNA translation, adaptation to cellular stress, tissue morphogenesis, cell cycle control, cell survival, and proliferation (1,12,13).…”

“…The CaMKKs have been studied most intensively in relationship to the function and development of excitable cells such as neurons, however, certain characteristics of the pathway raise the possibility that the arm of the CaM kinase cascade triggered by CaMKK2 (referred to here as the CaMKK2 pathway) may have a unique role(s) in nonexcitable cells (13). First, although present at much lower levels than in the CNS, CaMKK2 is expressed in many tissues and cell types (1,5). Second, whereas CaMKK1 is largely dependent for its activity on the presence of Ca 2ϩ /CaM, CaMKK2 shows considerable activity (ϳ70%) in the absence of Ca 2ϩ /CaM (5,16).…”

Repression of Ca2+/Calmodulin-dependent Protein Kinase IV Signaling Accelerates Retinoic Acid-induced Differentiation of Human Neuroblastoma Cells

“…In the adult, CaMKIV is expressed most abundantly in brain, testis, ovary, and T-lymphocytes (11). CaMKIV expression appears to be regulated during embryonic development.…”