A-kinase anchor proteins in endocrine systems and reproduction.

Center for Research on Reproduction and Women's Health, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Trends in Endocrinology and Metabolism (Impact Factor: 8.87). 01/2002; 12(10):434-40. DOI: 10.1016/S1043-2760(01)00493-3
Source: PubMed

ABSTRACT Over the past few years, significant progress has been made in characterizing the expression and localization of proteins that act as scaffolds for cAMP-dependent protein kinase (PK-A). These A-kinase anchor proteins (AKAPs) tether PK-A to intracellular organelles and structures, sequestering the kinase near its physiological substrates. The compartmentalization of distinct pockets of PK-A activity serves to provide spatial regulation of this signaling pathway. In addition, other signaling proteins bind to AKAPs, as do some newly described proteins of unknown function, suggesting that proteins of various pathways are anchored through AKAPs.

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    • "In S. aurata, an AKAP protein that anchors the regulatory subunit of PKA for tethering of protein kinases in close proximity to their target proteins has been identified. Different types of AKAP have been found in spermatozoa, localized into the fibrous sheath of the principal piece (Moss and Gerton 2001). In mammals, it has been demonstrated that, among the proteins phosphorylated during epididymal maturation, there are several mitochondrial proteins (Aitken et al. 2007) and a protein phospahatase PP1γ2 (Chakrabarti et al. 2007). "
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    ABSTRACT: In many marine fish species, the spermatozoa are immotile in the testis and seminal plasma, and motility is induced when they are released in the aqueous environment. It is well known that the extracellular factors (hyperosmolality or sperm-activating peptides), controlling sperm motility in marine fish, act on the axonemal apparatus through signal transduction across the plasma membrane. To better understand the molecular mechanism regulating axoneme activation in marine fish, the present review examines the existing literature, with particular emphasis on protein phosphorylation/dephosphorylation process. The present review suggests that: (1) there is no single model that can explain the molecular activation and regulation of sperm motility of the marine fish; (2) only in some species (puffer fish, tilapia, gilthead sea bream, and striped sea bream) protein phosphorylation/dephosphorylation has been shown to be involved in flagellar motility regulation; (3) only a few proteins were identified, which show a change in their state of phosphorylation following sperm activation. A model of molecular mechanism controlling the activation of sperm motility in gilthead sea bream is being proposed here, which could be a useful model to clarify the sperm motility activation process in other species.
    01/2012; 4(1). DOI:10.1186/2008-6970-4-2
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    • "So far, cAMP/PKA seems to play a key role in the mechanisms that trigger capacitation and the associated P-Tyr in all the mammalian species studied [11,26,27,72,88–91]. Of interest, the proteins subjected to P-Tyr during capacitation are AKAPs and the major proteins of the fibrous sheath, the cytoskeletal structure surrounding the axoneme and outer dense fibers of mammalian sperm flagellum [17] [92] [93]. AKAPs act as scaffolds for signaling elements, such as PKA, calmodulin, and PKC [94]. "
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    ABSTRACT: The role of reactive oxygen species (ROS) as signal transduction elements in physiological phenomena is a recent concept that changes the paradigm of these active species as harmful molecules that promote deleterious effects and even cell death. Capacitation is a term used to define a complex and not well-characterized process that allows spermatozoa to complete their preparation to fertilize oocytes. Spermatozoa from many species incubated under specific conditions have the ability to produce small amounts of ROS without harming cell function and rather promoting signal transduction pathways associated with capacitation. This review summarizes the findings regarding the role of ROS during mammalian sperm capacitation, specifically as physiological mediators that trigger phosphorylation events. The role of ROS as regulators of protein tyrosine phosphorylation has been known for a decade but other novel phosphorylations, such as those of PKA substrates, of MEK-like proteins, and of proteins with the threonine-glutamine-tyrosine motif, were recently evidenced. Here we stress the involvement of PKA and the ERK pathway as two signal mechanisms acting independently that contribute to the modulation of protein tyrosine phosphorylation required for spermatozoa to achieve capacitation. Moreover, integration of all these data reinforces the concept that although some phosphorylation events are independent of the others, cross talk is also needed among the various pathways involved.
    Free Radical Biology and Medicine 09/2006; 41(4):528-40. DOI:10.1016/j.freeradbiomed.2006.04.027 · 5.71 Impact Factor
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    • "The major component of the mouse sperm FS is AKAP4. AKAPs and their interacting proteins in the mammalian flagella have been reviewed (Moss and Gerton, 2001; Eddy et al., 2003). AKAPs form complexes with other components of the signal-transduction pathways. "
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    ABSTRACT: To date, 21 knockout mouse models are known to bear specific anomalies of the sperm flagellum structures leading to motility disorders. In addition, genes responsible for flagellar defects of two well-known spontaneous mutant mice have recently been identified. These models reveal genetic factors, which are required for the proper assembly of the axoneme, the annulus, the mitochondrial sheath and the fibrous sheath. Many of these genetic factors follow unexpected cellular pathways to act on sperm flagellum morphogenesis. These mouse models may bear anomalies which are restricted to the spermatozoa or display more complex phenotypes that often include neuropathies and/or cilia-related diseases. In human, several structural disorders of the sperm flagellum found in brothers or consanguineous men probably have a genetic origin, but the genes involved have not yet been identified. The mutant mice we present in this review are invaluable models, which can be used to identify potential candidate genes for infertile men with specific sperm flagellum anomalies.
    Human Reproduction Update 03/2006; 12(4):449-61. DOI:10.1093/humupd/dml013 · 8.66 Impact Factor
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