Dual control of cell growth by somatomedins and platelet-derived growth factor.

Abstract

Quiescent BALB/c 3T3 cells exposed briefly to a platelet-derived growth factor (PDGF) become "competent" to replicate their DNA but do not "progress" into S phase unless incubated with growth factors contained in platelet-poor plasma. Plasma from hypophysectomized rats is deficient in progression activity; it does not stimulate PDGF-treated competent cells to synthesize DNA. Addition of somatomedin C to hypophysectomized rat plasma stimulates competent cells to synthesize DNA, demonstrating that somatomedin C is required for progression. Various growth factors were tested for progression activity and competence activity by using BALB/c 3T3 tissue culture assays. Multiplication stimulating activity and other members of the somatomedin family of growth factors are (like somatomedin C) potent mediators of progression. Other mitogenic agents, such as fibroblast growth factor, are (like PDGF) potent inducers of competence. Growth factors with potent progression activity have little or no competence activity and vice versa. In contrast, simian virus 40 provides both competence and progession activity. Coordinate control of BALB/c 3T3 cell growth in vitro by competence factors and somatomedins may be a specific example of a common pattern for growth regulation in animal tissues.

Connecting signaling and cell cycle progression in growth factor-stimulated cells

“…Using subsaturating concentrations of growth factors, Pledger, Stiles, Antoniades, and Sher demonstrated that in Balb/c 3T3s cell cycle progression required the input of two di erent types of factors (Pledger et al, 1977(Pledger et al, , 1978Stiles et al, 1979b). Growth factors such as PDGF or FGF made the cells competent, but did not drive them into S phase.…”

Possible involvement of protein kinase C in proliferation and differentiation of osteoblast‐like cells

“…There is ample evidence indicating that two sets of growth factors, namely 'competence factors' and 'progression factors', successively and synergistically promote the proliferation of cells [16]. In the case of fibroblasts, platelet-derived growth factor and fibroblast growth factor that process cells from Go to G~ phase, belong to the competence factors, whereas insulin, epidermal growth factor and IGF-I that induce progression of cells from G~ to S phase, belong to the progression factors [17].…”

Heterogeneous activation of protein kinase C during rat liver regeneration induced by carbon tetrachloride administration

“…Some of the hepatotrophic factors would cause the receptor-mediated hydrolysis of inositol phospholipids, resulting in activation of PKC. Vasopressin, angiotensin and epinephrine, defined as competence factors for cellular growth [15], may activate PKC, and then the activated PKC may mediate the sequence of early events in cellular proliferation of the liver, as speculated for various tissues and cell lines [6,16-2 11. In addition, the activated PKC modulates binding and the phosphorylation of receptors for EGF [22,23], which is defined as a progression factor [15].…”

“…Vasopressin, angiotensin and epinephrine, defined as competence factors for cellular growth [15], may activate PKC, and then the activated PKC may mediate the sequence of early events in cellular proliferation of the liver, as speculated for various tissues and cell lines [6,16-2 11. In addition, the activated PKC modulates binding and the phosphorylation of receptors for EGF [22,23], which is defined as a progression factor [15]. The modulation of the EGF receptor by PKC may provide a mechanism whereby competence factor(s) and progression factor(s) can act sequentially in stimulating cell growth.…”