The EGF-like homeotic protein dlk affects cell growth and interacts with growth-modulating molecules in the yeast two-hybrid system.
Levels of dlk, an EGF-like homeotic protein, are critical for several differentiation processes. Because growth and differentiation are, in general, exclusive of each other, and increasing evidence indicates that Dlk1 expression changes in tumorigenic processes, we studied whether dlk could also affect cell growth. We found that, in response to glucocorticoids, Balb/c 3T3 cells with diminished levels of dlk expression develop foci-like cells that have lost contact inhibition, display altered morphology, and grow faster than control cell lines. Balb/c 3T3 cells spontaneously growing more rapidly are also dlk-negative cells. Moreover, screening by the yeast two-hybrid system, using Dlk1 constructs as baits, resulted in the isolation of GAS1 and acrogranin cDNAs. Interestingly, these proteins are cysteine-rich molecules involved in the control of cell growth. Taken together, these observations suggest that dlk may participate in a network of interactions controlling how the cells respond to growth or differentiation signals.
Baladrón
Victoriano
V
Laboratory of Immunobiology, Division of Monoclonal Antibodies, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, Maryland 20852, USA.
Ruiz-Hidalgo
María José
MJ
Bonvini
Ezio
E
Gubina
Elena
E
Notario
Vicente
V
Laborda
Jorge
J
D016475:3T3 Cells; D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000235:genetics; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000077155:Granulins; D006133:Growth Substances; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000077153:Progranulins; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000096:biosynthesis; D020449:Repetitive Sequences, Amino Acid; D020798:Two-Hybrid System Techniques; D015003:Yeasts / Q000235:genetics
D018797:Cell Cycle Proteins; C096192:GAS1 protein, human; D058851:GPI-Linked Proteins; C492314:GRN protein, human; C501180:Gas1 protein, mouse; D006023:Glycoproteins; D000077155:Granulins; C120204:Grn protein, mouse; D006133:Growth Substances; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000077153:Progranulins; D012333:RNA, Messenger; C064045:delta protein; D004815:Epidermal Growth Factor