Mitogenic factor

Figure 38-7. Activation of elF-4E by insulin and formation of the cap binding elF-4F complex. The 4F-cap mRNA complex is depicted as in Figure 38-6. The 4F complex consists of elF-4E (4E), elF-4A, and elF-4G. 4E is inactive when bound by one ofa family of binding proteins (4E-BPs). Insulin and mitogenic factors (eg, IGF-1, PDGF, interleukin-2, and angiotensin II) activate a serine protein kinase in the mTOR pathway, and this results in the phosphorylation of 4E-BP. Phosphorylated 4E-BP dissociates from 4E, and the latter is then able to form the 4F complex and bind to the mRNA cap. These growth peptides also phosphorylate 4E itself by activating a component of the MAP kinase pathway. Phosphorylated 4E binds much more avidly to the cap than does nonphosphorylated 4E.

Thymocyte stimulating factor [NAM SY] Lymphocyte mitogenic factor [NAM SY] Macrolin [NAM TR used in France, perhaps other European countries]... 

Terada, S., Sasaki, M., Yanagihara, K., and Yamada, H. "Preparation of silk protein sericin as mitogenic factor for better mammalian cell culture". ]. Biosci. Bioeng. 100(6), 667-671 (2005). 

Mitogenic factors acting on mesenchymal cells, e.g. fibroblasts, glial cells, muscle cells... 

Some progress has been reported toward the preparation of an antiserum with specificity toward lymphokines that influence macrophage functio g, and also toward products participating in mixed lymphocyte responses. Antibodies prepared agai gt guinea pig lymphotoxin did not neutralize mitogenic factor or MIF. Mouse lymphotoxin has been characterize as a molecule of 41,000 daltons with an isoelectric point of 4.4 to 4.8. 

Tang DG, Renaud C, Stojakovic S, Diglio CA, Porter A, Honn KV. 12(S)-HETE is a mitogenic factor for microvascular endothelial cells its potential role in angiogenesis. Biochem Biophys Res Commun. 211 (1995b) 462-468. 

Wille, 1975). The division cycle occurs in these cells with a periodicity close to 12 h. Mixing experiments relying on the fusion of plasmodia taken at different times over the cycle showed phase advances or delays that would be typical of the behaviour expected if mitosis were driven by a continuous oscillator of a moderate relaxation nature (Kauffman, 1974 Kauffman Wille, 1975 Wille, Scheffey Kau an, 1977). Implicit in the limit cycle description is the assumption that one of the variables of the oscillator behaves as a mitogenic factor once this variable exceeds a certain threshold, mitosis would ensue. A specific prediction of the limit cycle model of mitosis is that finely tuned perturbations may transiently suppress oscillations. In this case, mitosis would eventually resume, with undefined phase, possibly after a delay corresponding to a few cycles in which the mitogenic factor oscillates below its threshold level. As the trajectory followed by the oscillator eventually approaches the asymptotic limit cycle, mitosis would occur when the threshold is again exceeded. 

An alternative view holds that cell division is brought about by the accumulation of a mitogenic factor that, above some threshold, triggers mitosis the latter, discontinuous event brings this factor back to a low value and a new cycle starts as the accumulation of the mitogenic factor resumes. Models of such a discontinuous nature (Fantes et al, 1975) differ in several respects from the continuous biochemical oscillatory mechanism for a comparative discussion of the two classes of mechanism, see Tyson Sachsenmaier (1978) and Winfree (1980,1984). 

Weak activation of the mitogen-activated kinases ERKl/2 and p38 in primary human monocytes. Three major MAPK pathways are known, ERKl/2, JNK, and p38, which further on leads to the phosphorylation of cytoplasmic and nuclear targets. ERK is mostly activated by mitogenic factors, whereas INK and p38 are usually activated by stress-inducing stimuli such as UV light MAPKs have, in general, an important role in cell proliferation [25]. 

StoutRW. Insulin as a mitogenic factor role in the pathogenesis of cardiovascular disease. Am J Med 1991 90 62S-65S. 

Figure 6.1a B lymphocyte from a patient with common variable hypogammaglobulinaemia following exposure to the T cell mitogenic factor. This B lymphocyte shows no response.

Figure 6.1b B lymphocyte from a patient with common variable hypogammaglobulinaemia following exposure to the T cell mitogenic factor. The cell shows a response in new development of endoplasmic reticulum and enlargement of the nucleus but it has failed to secrete newly synthesized y-globulin. Magnification x 10 200 (from Geha et aL, New Eng. J. Med. 291, by courtesy of the publishers).

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