Table of Contents

October 2002; 2 (6)




  • Although phospholipase C-γ (PLC-γ) participates in cellular mitogenesis, evidence indicates that the catalytic activity of PLC-γ (to hydrolyze certain phosphoinositides) is nonessential to the process. So how is it that PLC-γ is necessary but its lipase activity is not? Recently published results from Snyder and colleagues describe the ability of PLC-γ to facilitate guanine nucleotide exchange for the recently identified nucleus-localized GTPase PIKE, which acts to enhance the enzymatic activity of phosphatidylinositol 3′-kinase (PI3K). The authors contend that the SH3 domain, rather than the catalytic domain, of PLC-γ is required for aiding PIKE, and furthermore, that the mitogenic activity of PLC-γ depends not on its phospholipase activity, but rather on its interaction with PIKE. Wang and Moran examine the results and piece together a picture of how PLC-γ cooperates with PIKE.

  • In T lymphocytes, the “novel” protein kinase C ?? (PKC ??) isoform and the transcription factor nuclear factor-κB (NF-κB) are required for cell proliferation and the production of cytokines in response to T cell activation; however, the molecular interactions that link PKC?? and NF-κB have remained unknown. Two recent reports demonstrate that CARMA1 (caspase recruitment domain-containing membrane-associated guanylate kinase protein-1) bridges the gap between PKC?? and the IκB kinase (IKK)-dependent activation of NF-κB in T cells. Excessive T lymphocyte activation and proliferation are hallmarks of T cell-derived leukemias. Given that CARMA1 is specifically expressed in lymphoid tissues, could pharmacological inhibitors be designed to inhibit CARMA1’s (or PKC??’s) ability to promote the activation of NF-κB?

  • The presence or absence of estrogen receptor (ER) expression in tumor cells affects prognosis and guides treatment choices. Kumar et al. suggest that a shortened form of the metastatic tumor antigen 1 (MTA1s) acts to sequester the estrogen receptor (ER) in the cytoplasm, inhibiting its ability to transactivate specific genes and, presumably, adding to the ER’s ability to transduce non-genomic (cytoplasmic) signaling mechanisms. However, if the cancer is negative for ERα in the nucleus, but is positive for ERα in the cytoplasm, how does this sequestration affect the treatment of the patient or our understanding of the disease process? Cheng et al. caution that these results must be interpreted carefully with regard to what is known about estrogen-dependent and -independent tumor growth and chemotherapeutic strategies to destroy them.


  • Despite important inroads into the molecular pathology of Alzheimer disease, effective long-term treatment for the condition remains elusive. Among the many gene products that are recognized as factors in the disease is apolipoprotein E (apoE). The risk that specific isoforms of apoE pose with regard to Alzheimer Disease clearly varies, and so the roles that apoE plays in the brain will be crucial to a full understanding of the disease and to efforts to develop effective therapies.

  • Our understanding of the molecular underpinnings of human cognition has been greatly aided by the convergent synergy of clinical, genetic, and signaling research. By identifying the mutated genes that give rise to syndromes of mental retardation or cognitive defects in patients, and by placing the associated gene products within signaling networks, researchers are piecing together how learning occurs and how memories are formed and sustained.

  • The perception of pain is highly complex, and requires neural integration from a variety of routes. Spinal pathways to the amygdala, hypothalamus, reticular formation, medial thalamic nuclei, and limbic cortical structures transmit information involved in arousal, bodily regulation, and emotional responses. Other, albeit indirect, pathways can carry signals to these same structures, for example, from spinal pathways to somatosensory thalamic and cortical areas, and from these areas to cortical limbic structures. Indirect cortico-limbic pathways integrate nociception with information about the status of the body and self to provide cognitive mediation of pain affect. Both direct and indirect routes must culminate in the prioritization of emotions and responses to pain.

Beyond the Bench

Net Results