Long bone growth in children is dependent on the constant and consistent development of chondrocytes at the growth plate. Epiphyseal chondrocytes achieve growth first through an increase in cell number, or proliferation, and then by the accumulation of glycogen which results in significant cellular hypertrophy. This ordered pattern of differentiation is regulated by a long list of both systemic and locally derived factors, not the least of which is growth hormone (GH). The somatomedin hypothesis was originally put forth to describe how systemic GH, by stimulating the hepatic production of insulin-like growth factor (IGF-I), positively affects long bone growth. More recent studies have suggested that GH acts locally at the growth plate, both directly and in an autocrine manner by stimulating IGF-I synthesis by the chondrocytes themselves. IGF-I is known to utilize protein kinase cascades in multiple different cell types, but surprisingly little is known about which intracellular signaling mechanisms are employed by GH and IGF-I in growth plate chondrocytes. We propose to study the role of the various mitogen-activated protein kinase (MAPK) pathways in the regulation of chondrocyte proliferation and hypertrophy by GH and IGF-I.
RESEARCH INTERESTS
Growth Disorders
Skeletal Dysplasias
RECENT PUBLICATIONS
Berman KS, Hutchison M, Avery L, Cobb MH, "kin-18, a C. elegans protein kinase involved in feeding" Gene, 279(2):137-147, November 2001
Chen Z, Hutchison M, Cobb MH, "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain" Journal of Biological Chemistry, 274(40):28803-28807, October 1999
Hutchison M, Berman KS, Cobb MH, "Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades" Journal of Biological Chemistry, 273(44):28625-28632, October 1998
Frost JA, Xu S, Hutchison MR, Marcus S, Cobb MH, "Actions of Rho family small G proteins and p21-activated protein kinases on mitogen-activated protein kinase family members" Molecular & Cellular Biology, 16(7):3707-3713, July 1996
Polverino A, Frost J, Yang P, Hutchison M, Neiman AM, Cobb MH et al, "Activation of mitogen-activated protein kinase cascades by p21-activated protein kinases in cell-free extracts of Xenopus oocytes" Journal of Biological Chemistry, 270(44):26067-26070, November 1995
SIGNIFICANT PUBLICATIONS
Cobb MH, Xu S, Hepler JE, Hutchison M, Frost J, Robbins DJ, "Regulation of the MAP kinase cascade" Cellular & Molecular Biology Research, 40(3):253-256, 1994
Gama Sosa MA, Rosas DH, DeGasperi R, Morita E, Hutchison MR, Ruprecht RM, "Negative regulation of the 5’ long terminal repeat (LTR) by the 3’ LTR in the murine proviral genome" Journal of Virology, 68(4):2662-2670, 1994
Wolfson AJ, Hutchison MR, Andrews JS, Merriam KJ, "Effects of charcoal on dissociation kinetics of nuclear and cytosolic steroid-receptor complexes from hen oviduct" Journal of Receptor Research, 10(3-4):137-148, 1990
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